diff --git a/runtime/BUILD.gn b/runtime/BUILD.gn
index 81af36d1732..730c50613f5 100644
--- a/runtime/BUILD.gn
+++ b/runtime/BUILD.gn
@@ -169,7 +169,7 @@ config("dart_arch_config") {
     assert(false)
   }
   if (dart_force_simulator) {
-    defines += [ "USING_SIMULATOR" ]
+    defines += [ "DART_INCLUDE_SIMULATOR" ]
     if (dart_target_arch == "arm64") {
       defines += [ "SIMULATOR_FFI" ]
     }
diff --git a/runtime/bin/snapshot_utils.cc b/runtime/bin/snapshot_utils.cc
index 038d87aec93..79543bf19e8 100644
--- a/runtime/bin/snapshot_utils.cc
+++ b/runtime/bin/snapshot_utils.cc
@@ -25,14 +25,14 @@
 
 #define LOG_SECTION_BOUNDARIES false
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
 #if defined(DART_HOST_OS_LINUX) || defined(DART_HOST_OS_ANDROID) ||            \
     defined(DART_HOST_OS_FUCHSIA)
 #define NATIVE_SHARED_OBJECT_FORMAT_ELF 1
 #elif defined(DART_HOST_OS_MACOS)
 #define NATIVE_SHARED_OBJECT_FORMAT_MACHO 1
 #endif
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 namespace dart {
 namespace bin {
@@ -215,7 +215,7 @@ static AppSnapshot* TryReadAppSnapshotDynamicLibrary(
     DartUtils::MagicNumber magic_number,
     const char* script_name,
     const char** error) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   *error = "running on a simulated architecture";
   return nullptr;
 #else
@@ -277,7 +277,7 @@ static AppSnapshot* TryReadAppSnapshotDynamicLibrary(
   return new DylibAppSnapshot(magic_number, library, vm_data_buffer,
                               vm_instructions_buffer, isolate_data_buffer,
                               isolate_instructions_buffer);
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 }
 
 class ElfAppSnapshot : public AppSnapshot {
diff --git a/runtime/lib/ffi_dynamic_library.cc b/runtime/lib/ffi_dynamic_library.cc
index 5fb31a302a4..0aefcee4b5f 100644
--- a/runtime/lib/ffi_dynamic_library.cc
+++ b/runtime/lib/ffi_dynamic_library.cc
@@ -29,11 +29,11 @@
 
 namespace dart {
 
-#if (defined(USING_SIMULATOR) && !defined(SIMULATOR_FFI)) ||                   \
+#if (defined(DART_INCLUDE_SIMULATOR) && !defined(SIMULATOR_FFI)) ||            \
     (defined(DART_PRECOMPILER) && !defined(TESTING))
 
 DART_NORETURN static void SimulatorUnsupported() {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   Exceptions::ThrowUnsupportedError("Not supported on this simulator.");
 #else
   Exceptions::ThrowUnsupportedError("Not supported in precompiler.");
@@ -66,7 +66,7 @@ DEFINE_NATIVE_ENTRY(Ffi_GetFfiNativeResolver, 1, 0) {
   SimulatorUnsupported();
 }
 
-#else  // defined(USING_SIMULATOR) ||                                          \
+#else  // defined(DART_INCLUDE_SIMULATOR) ||                                   \
        // (defined(DART_PRECOMPILER) && !defined(TESTING))
 
 // If an error occurs populates |error| (if provided) with an error message
@@ -516,7 +516,7 @@ DEFINE_NATIVE_ENTRY(Ffi_GetFfiNativeResolver, 1, 0) {
   return Pointer::New(reinterpret_cast<intptr_t>(FfiResolve));
 }
 
-#endif  // (defined(USING_SIMULATOR) && !defined (SIMULATOR_FFI)) ||           \
+#endif  // (defined(DART_INCLUDE_SIMULATOR) && !defined (SIMULATOR_FFI)) ||    \
         // (defined(DART_PRECOMPILER) && !defined(TESTING))
 
 }  // namespace dart
diff --git a/runtime/platform/globals.h b/runtime/platform/globals.h
index 04c13c54e9c..6ae592148de 100644
--- a/runtime/platform/globals.h
+++ b/runtime/platform/globals.h
@@ -368,30 +368,30 @@ struct simd128_value_t {
 // Determine whether we will be using the simulator.
 #if defined(TARGET_ARCH_IA32)
 #if !defined(HOST_ARCH_IA32)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #elif defined(TARGET_ARCH_X64)
 #if !defined(HOST_ARCH_X64)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #elif defined(TARGET_ARCH_ARM)
 #if !defined(HOST_ARCH_ARM)
 #define TARGET_HOST_MISMATCH 1
 #if !defined(IS_SIMARM_HOST64)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #endif
 #elif defined(TARGET_ARCH_ARM64)
 #if !defined(HOST_ARCH_ARM64)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #elif defined(TARGET_ARCH_RISCV32)
 #if !defined(HOST_ARCH_RISCV32)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #elif defined(TARGET_ARCH_RISCV64)
 #if !defined(HOST_ARCH_RISCV64)
-#define USING_SIMULATOR 1
+#define DART_INCLUDE_SIMULATOR 1
 #endif
 #else
 #error Unknown architecture.
diff --git a/runtime/vm/compiler/assembler/assembler_arm.cc b/runtime/vm/compiler/assembler/assembler_arm.cc
index b0aa28a065d..c576660e712 100644
--- a/runtime/vm/compiler/assembler/assembler_arm.cc
+++ b/runtime/vm/compiler/assembler/assembler_arm.cc
@@ -15,8 +15,9 @@
 #include "vm/tags.h"
 
 // An extra check since we are assuming the existence of /proc/cpuinfo below.
-#if !defined(USING_SIMULATOR) && !defined(__linux__) && !defined(ANDROID) &&   \
-    !defined(DART_HOST_OS_IOS) && !defined(DART_HOST_OS_MACOS)
+#if !defined(DART_INCLUDE_SIMULATOR) && !defined(__linux__) &&                 \
+    !defined(ANDROID) && !defined(DART_HOST_OS_IOS) &&                         \
+    !defined(DART_HOST_OS_MACOS)
 #error ARM cross-compile only supported on Linux, Android, iOS, and Mac
 #endif
 
diff --git a/runtime/vm/compiler/assembler/assembler_arm_test.cc b/runtime/vm/compiler/assembler/assembler_arm_test.cc
index 7f9695b3434..931f56ce8e0 100644
--- a/runtime/vm/compiler/assembler/assembler_arm_test.cc
+++ b/runtime/vm/compiler/assembler/assembler_arm_test.cc
@@ -1871,7 +1871,7 @@ ASSEMBLER_TEST_RUN(Sdiv_corner, test) {
 }
 
 ASSEMBLER_TEST_GENERATE(IntDiv_supported, assembler) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   bool orig = TargetCPUFeatures::integer_division_supported();
   HostCPUFeatures::set_integer_division_supported(true);
   __ mov(R0, Operand(27));
@@ -1889,7 +1889,7 @@ ASSEMBLER_TEST_GENERATE(IntDiv_supported, assembler) {
 
 ASSEMBLER_TEST_RUN(IntDiv_supported, test) {
   EXPECT(test != nullptr);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   bool orig = TargetCPUFeatures::integer_division_supported();
   HostCPUFeatures::set_integer_division_supported(true);
   typedef int (*Tst)() DART_UNUSED;
@@ -1902,7 +1902,7 @@ ASSEMBLER_TEST_RUN(IntDiv_supported, test) {
 }
 
 ASSEMBLER_TEST_GENERATE(IntDiv_unsupported, assembler) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   bool orig = TargetCPUFeatures::integer_division_supported();
   HostCPUFeatures::set_integer_division_supported(false);
   __ mov(R0, Operand(27));
@@ -1920,7 +1920,7 @@ ASSEMBLER_TEST_GENERATE(IntDiv_unsupported, assembler) {
 
 ASSEMBLER_TEST_RUN(IntDiv_unsupported, test) {
   EXPECT(test != nullptr);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   bool orig = TargetCPUFeatures::integer_division_supported();
   HostCPUFeatures::set_integer_division_supported(false);
   typedef int (*Tst)() DART_UNUSED;
diff --git a/runtime/vm/compiler/assembler/assembler_riscv_test.cc b/runtime/vm/compiler/assembler/assembler_riscv_test.cc
index e9cfccaeed1..86f36c1f288 100644
--- a/runtime/vm/compiler/assembler/assembler_riscv_test.cc
+++ b/runtime/vm/compiler/assembler/assembler_riscv_test.cc
@@ -50,7 +50,7 @@ static intx_t Call(intx_t entry,
                    intx_t arg1 = 0,
                    intx_t arg2 = 0,
                    intx_t arg3 = 0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->Call(entry, arg0, arg1, arg2, arg3);
 #else
   typedef intx_t (*F)(intx_t, intx_t, intx_t, intx_t);
@@ -58,7 +58,7 @@ static intx_t Call(intx_t entry,
 #endif
 }
 static float CallF(intx_t entry, intx_t arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0);
 #else
   typedef float (*F)(intx_t);
@@ -66,7 +66,7 @@ static float CallF(intx_t entry, intx_t arg0) {
 #endif
 }
 static float CallF(intx_t entry, intx_t arg0, float arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0, arg1);
 #else
   typedef float (*F)(intx_t, float);
@@ -74,7 +74,7 @@ static float CallF(intx_t entry, intx_t arg0, float arg1) {
 #endif
 }
 static float CallF(intx_t entry, double arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0);
 #else
   typedef float (*F)(double);
@@ -82,7 +82,7 @@ static float CallF(intx_t entry, double arg0) {
 #endif
 }
 static float CallF(intx_t entry, float arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0);
 #else
   typedef float (*F)(float);
@@ -90,7 +90,7 @@ static float CallF(intx_t entry, float arg0) {
 #endif
 }
 static float CallF(intx_t entry, float arg0, float arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0, arg1);
 #else
   typedef float (*F)(float, float);
@@ -98,7 +98,7 @@ static float CallF(intx_t entry, float arg0, float arg1) {
 #endif
 }
 static float CallF(intx_t entry, float arg0, float arg1, float arg2) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallF(entry, arg0, arg1, arg2);
 #else
   typedef float (*F)(float, float, float);
@@ -106,7 +106,7 @@ static float CallF(intx_t entry, float arg0, float arg1, float arg2) {
 #endif
 }
 static intx_t CallI(intx_t entry, float arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallI(entry, arg0);
 #else
   typedef intx_t (*F)(float);
@@ -114,7 +114,7 @@ static intx_t CallI(intx_t entry, float arg0) {
 #endif
 }
 static intx_t CallI(intx_t entry, float arg0, float arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallI(entry, arg0, arg1);
 #else
   typedef intx_t (*F)(float, float);
@@ -122,7 +122,7 @@ static intx_t CallI(intx_t entry, float arg0, float arg1) {
 #endif
 }
 static double CallD(intx_t entry, intx_t arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0);
 #else
   typedef double (*F)(intx_t);
@@ -131,7 +131,7 @@ static double CallD(intx_t entry, intx_t arg0) {
 }
 #if XLEN == 32
 static double CallD(intx_t entry, int64_t arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0);
 #else
   typedef double (*F)(int64_t);
@@ -140,7 +140,7 @@ static double CallD(intx_t entry, int64_t arg0) {
 }
 #endif
 static double CallD(intx_t entry, intx_t arg0, double arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0, arg1);
 #else
   typedef double (*F)(intx_t, double);
@@ -148,7 +148,7 @@ static double CallD(intx_t entry, intx_t arg0, double arg1) {
 #endif
 }
 static double CallD(intx_t entry, float arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0);
 #else
   typedef double (*F)(float);
@@ -156,7 +156,7 @@ static double CallD(intx_t entry, float arg0) {
 #endif
 }
 static double CallD(intx_t entry, double arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0);
 #else
   typedef double (*F)(double);
@@ -164,7 +164,7 @@ static double CallD(intx_t entry, double arg0) {
 #endif
 }
 static double CallD(intx_t entry, double arg0, double arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0, arg1);
 #else
   typedef double (*F)(double, double);
@@ -172,7 +172,7 @@ static double CallD(intx_t entry, double arg0, double arg1) {
 #endif
 }
 static double CallD(intx_t entry, double arg0, double arg1, double arg2) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallD(entry, arg0, arg1, arg2);
 #else
   typedef double (*F)(double, double, double);
@@ -180,7 +180,7 @@ static double CallD(intx_t entry, double arg0, double arg1, double arg2) {
 #endif
 }
 static intx_t CallI(intx_t entry, double arg0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallI(entry, arg0);
 #else
   typedef intx_t (*F)(double);
@@ -188,7 +188,7 @@ static intx_t CallI(intx_t entry, double arg0) {
 #endif
 }
 static intx_t CallI(intx_t entry, double arg0, double arg1) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallI(entry, arg0, arg1);
 #else
   typedef intx_t (*F)(double, double);
@@ -197,7 +197,7 @@ static intx_t CallI(intx_t entry, double arg0, double arg1) {
 }
 #if XLEN == 32
 static int64_t CallI64(intx_t entry, double arg0, double arg1 = 0.0) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   return Simulator::Current()->CallI64(entry, arg0, arg1);
 #else
   typedef int64_t (*F)(double, double);
diff --git a/runtime/vm/compiler/stub_code_compiler_arm.cc b/runtime/vm/compiler/stub_code_compiler_arm.cc
index 749be9cf068..bdeced03601 100644
--- a/runtime/vm/compiler/stub_code_compiler_arm.cc
+++ b/runtime/vm/compiler/stub_code_compiler_arm.cc
@@ -311,7 +311,7 @@ void StubCodeCompiler::GenerateLoadFfiCallbackMetadataRuntimeFunction(
 }
 
 void StubCodeCompiler::GenerateFfiCallbackTrampolineStub() {
-#if defined(USING_SIMULATOR) && !defined(DART_PRECOMPILER)
+#if defined(DART_INCLUDE_SIMULATOR) && !defined(DART_PRECOMPILER)
   // TODO(37299): FFI is not supported in SIMARM.
   __ Breakpoint();
 #else
diff --git a/runtime/vm/compiler/stub_code_compiler_arm64.cc b/runtime/vm/compiler/stub_code_compiler_arm64.cc
index bed546c1a37..c49e1273291 100644
--- a/runtime/vm/compiler/stub_code_compiler_arm64.cc
+++ b/runtime/vm/compiler/stub_code_compiler_arm64.cc
@@ -76,7 +76,7 @@ void StubCodeCompiler::EnsureIsNewOrRemembered() {
 // [Thread::tsan_utils_->setjmp_buffer_]).
 static void WithExceptionCatchingTrampoline(Assembler* assembler,
                                             std::function<void()> fun) {
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
   const Register kTsanUtilsReg = R3;
 
   // Reserve space for arguments and align frame before entering C++ world.
@@ -147,11 +147,11 @@ static void WithExceptionCatchingTrampoline(Assembler* assembler,
     __ Bind(&do_native_call);
     __ MoveRegister(kSavedRspReg, SP);
   }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
   fun();
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_target_thread_sanitizer) {
     __ MoveRegister(SP, kSavedRspReg);
     __ AddImmediate(SP, kJumpBufferSize);
@@ -161,7 +161,7 @@ static void WithExceptionCatchingTrampoline(Assembler* assembler,
     __ str(TMP,
            Address(kTsanUtilsReg2, target::TsanUtils::setjmp_buffer_offset()));
   }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 }
 
 // Input parameters:
diff --git a/runtime/vm/compiler/stub_code_compiler_riscv.cc b/runtime/vm/compiler/stub_code_compiler_riscv.cc
index b8cbed3de04..49bf14000a6 100644
--- a/runtime/vm/compiler/stub_code_compiler_riscv.cc
+++ b/runtime/vm/compiler/stub_code_compiler_riscv.cc
@@ -322,7 +322,7 @@ void StubCodeCompiler::GenerateLoadFfiCallbackMetadataRuntimeFunction(
 }
 
 void StubCodeCompiler::GenerateFfiCallbackTrampolineStub() {
-#if defined(USING_SIMULATOR) && !defined(DART_PRECOMPILER)
+#if defined(DART_INCLUDE_SIMULATOR) && !defined(DART_PRECOMPILER)
   // TODO(37299): FFI is not supported in SIMRISCV32/64.
   __ ebreak();
 #else
diff --git a/runtime/vm/compiler/stub_code_compiler_x64.cc b/runtime/vm/compiler/stub_code_compiler_x64.cc
index e80ee335af6..0304d261640 100644
--- a/runtime/vm/compiler/stub_code_compiler_x64.cc
+++ b/runtime/vm/compiler/stub_code_compiler_x64.cc
@@ -79,7 +79,7 @@ void StubCodeCompiler::EnsureIsNewOrRemembered() {
 // [Thread::tsan_utils_->setjmp_buffer_]).
 static void WithExceptionCatchingTrampoline(Assembler* assembler,
                                             std::function<void()> fun) {
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
   const Register kTsanUtilsReg = RAX;
 
   // Reserve space for arguments and align frame before entering C++ world.
@@ -149,11 +149,11 @@ static void WithExceptionCatchingTrampoline(Assembler* assembler,
     __ Bind(&do_native_call);
     __ MoveRegister(kSavedRspReg, RSP);
   }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
   fun();
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_target_thread_sanitizer) {
     __ MoveRegister(RSP, kSavedRspReg);
     __ AddImmediate(RSP, Immediate(kJumpBufferSize));
@@ -161,7 +161,7 @@ static void WithExceptionCatchingTrampoline(Assembler* assembler,
     __ movq(kTsanUtilsReg2, Address(THR, target::Thread::tsan_utils_offset()));
     __ popq(Address(kTsanUtilsReg2, target::TsanUtils::setjmp_buffer_offset()));
   }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 }
 
 // Input parameters:
diff --git a/runtime/vm/cpu_arm64.cc b/runtime/vm/cpu_arm64.cc
index d435bf15ff5..9234831a05d 100644
--- a/runtime/vm/cpu_arm64.cc
+++ b/runtime/vm/cpu_arm64.cc
@@ -24,7 +24,7 @@ void CPU::FlushICache(uword start, uword size) {
 #if defined(DART_PRECOMPILED_RUNTIME)
   UNREACHABLE();
 #else
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     return;
   }
@@ -65,9 +65,9 @@ void CPU::FlushICache(uword start, uword size) {
 
 const char* CPU::Id() {
   return
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
       "sim"
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
       "arm64";
 }
 
@@ -76,7 +76,7 @@ const char* HostCPUFeatures::hardware_ = nullptr;
 bool HostCPUFeatures::initialized_ = false;
 #endif
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
   hardware_ = CpuInfo::GetCpuModel();
@@ -96,7 +96,7 @@ void HostCPUFeatures::Cleanup() {
   CpuInfo::Cleanup();
 }
 
-#else  // !defined(USING_SIMULATOR)
+#else  // !defined(DART_INCLUDE_SIMULATOR)
 
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
@@ -116,7 +116,7 @@ void HostCPUFeatures::Cleanup() {
   hardware_ = nullptr;
   CpuInfo::Cleanup();
 }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 }  // namespace dart
 
diff --git a/runtime/vm/cpu_ia32.cc b/runtime/vm/cpu_ia32.cc
index 8fe5a9c4724..fc60017203f 100644
--- a/runtime/vm/cpu_ia32.cc
+++ b/runtime/vm/cpu_ia32.cc
@@ -20,9 +20,9 @@ void CPU::FlushICache(uword start, uword size) {
 
 const char* CPU::Id() {
   return
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
       "sim"
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
       "ia32";
 }
 
diff --git a/runtime/vm/cpu_riscv.cc b/runtime/vm/cpu_riscv.cc
index e1440a9d2ee..361be8faa20 100644
--- a/runtime/vm/cpu_riscv.cc
+++ b/runtime/vm/cpu_riscv.cc
@@ -10,7 +10,7 @@
 
 #include "vm/cpuinfo.h"
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
 #if !defined(DART_HOST_OS_FUCHSIA)
 #include <sys/syscall.h>
 #else
@@ -28,7 +28,7 @@ namespace dart {
 void CPU::FlushICache(uword start, uword size) {
 #if defined(DART_PRECOMPILED_RUNTIME)
   UNREACHABLE();
-#elif !defined(USING_SIMULATOR)
+#elif !defined(DART_INCLUDE_SIMULATOR)
   // Nothing to do. Flushing no instructions.
   if (size == 0) {
     return;
@@ -53,9 +53,9 @@ void CPU::FlushICache(uword start, uword size) {
 
 const char* CPU::Id() {
   return
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
       "sim"
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 #if defined(TARGET_ARCH_RISCV32)
       "riscv32";
 #elif defined(TARGET_ARCH_RISCV64)
@@ -70,7 +70,7 @@ const char* HostCPUFeatures::hardware_ = nullptr;
 bool HostCPUFeatures::initialized_ = false;
 #endif
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
   hardware_ = CpuInfo::GetCpuModel();
@@ -90,7 +90,7 @@ void HostCPUFeatures::Cleanup() {
   CpuInfo::Cleanup();
 }
 
-#else  // !defined(USING_SIMULATOR)
+#else  // !defined(DART_INCLUDE_SIMULATOR)
 
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
@@ -110,7 +110,7 @@ void HostCPUFeatures::Cleanup() {
   hardware_ = nullptr;
   CpuInfo::Cleanup();
 }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 }  // namespace dart
 
diff --git a/runtime/vm/cpu_x64.cc b/runtime/vm/cpu_x64.cc
index e9c360302f5..942c8a62785 100644
--- a/runtime/vm/cpu_x64.cc
+++ b/runtime/vm/cpu_x64.cc
@@ -20,9 +20,9 @@ void CPU::FlushICache(uword start, uword size) {
 
 const char* CPU::Id() {
   return
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
       "sim"
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
       "x64";
 }
 
@@ -36,7 +36,7 @@ bool HostCPUFeatures::abm_supported_ = false;
 bool HostCPUFeatures::initialized_ = false;
 #endif
 
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
   hardware_ = CpuInfo::GetCpuModel();
@@ -60,7 +60,7 @@ void HostCPUFeatures::Cleanup() {
   CpuInfo::Cleanup();
 }
 
-#else  // !defined(USING_SIMULATOR)
+#else  // !defined(DART_INCLUDE_SIMULATOR)
 
 void HostCPUFeatures::Init() {
   CpuInfo::Init();
@@ -83,7 +83,7 @@ void HostCPUFeatures::Cleanup() {
   hardware_ = nullptr;
   CpuInfo::Cleanup();
 }
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 }  // namespace dart
 
diff --git a/runtime/vm/dart.cc b/runtime/vm/dart.cc
index 71fe736d38d..ba56a765f0f 100644
--- a/runtime/vm/dart.cc
+++ b/runtime/vm/dart.cc
@@ -386,7 +386,7 @@ char* Dart::DartInit(const Dart_InitializeParams* params) {
   TargetCPUFeatures::Init();
   FfiCallbackMetadata::Init();
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   Simulator::Init();
 #endif
   // Create the read-only handles area.
diff --git a/runtime/vm/dart_entry.cc b/runtime/vm/dart_entry.cc
index 9be9ccc3af2..496143b84c0 100644
--- a/runtime/vm/dart_entry.cc
+++ b/runtime/vm/dart_entry.cc
@@ -103,7 +103,7 @@ static ObjectPtr InvokeDartCode(uword entry_point,
   DartEntryScope dart_entry_scope(thread);
 
   const uword stub = StubCode::InvokeDartCode().EntryPoint();
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     auto invoke = [&](uword entry_point, uword arguments_descriptor,
                       uword arguments, Thread* thread) -> uword {
diff --git a/runtime/vm/exceptions.cc b/runtime/vm/exceptions.cc
index 667fcddd140..b1010480179 100644
--- a/runtime/vm/exceptions.cc
+++ b/runtime/vm/exceptions.cc
@@ -618,7 +618,7 @@ NO_SANITIZE_SAFE_STACK  // This function manipulates the safestack pointer.
     thread->set_execution_state(Thread::kThreadInGenerated);
   }
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   // Unwinding of the C++ frames and destroying of their stack resources is done
   // by the simulator, because the target stack_pointer is a simulated stack
   // pointer and not the C++ stack pointer.
diff --git a/runtime/vm/interpreter.cc b/runtime/vm/interpreter.cc
index 6373bb4f557..0df840d8163 100644
--- a/runtime/vm/interpreter.cc
+++ b/runtime/vm/interpreter.cc
@@ -583,7 +583,7 @@ DART_NOINLINE bool Interpreter::InvokeCompiled(Thread* thread,
   {
     InterpreterSetjmpBuffer buffer(this);
     if (!DART_SETJMP(buffer.buffer_)) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
       // We need to beware that bouncing between the interpreter and the
       // simulator may exhaust the C stack before exhausting either the
       // interpreter or simulator stacks.
diff --git a/runtime/vm/isolate.cc b/runtime/vm/isolate.cc
index 28060449db0..c3571cdb415 100644
--- a/runtime/vm/isolate.cc
+++ b/runtime/vm/isolate.cc
@@ -1869,7 +1869,7 @@ Isolate::~Isolate() {
 
   free(name_);
   delete field_table_;
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   delete simulator_;
 #endif
   delete message_handler_;
diff --git a/runtime/vm/native_arguments.h b/runtime/vm/native_arguments.h
index 1bbc371bfb9..5b98fab64c2 100644
--- a/runtime/vm/native_arguments.h
+++ b/runtime/vm/native_arguments.h
@@ -21,7 +21,7 @@ class Thread;
 
 #if defined(TESTING) || defined(DEBUG)
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 // The simulator/isolate might not exist yet for an async FFI callback, so do
 // not check. An equivalent check exists in the simulator itself.
 #define CHECK_STACK_ALIGNMENT                                                  \
diff --git a/runtime/vm/native_entry.cc b/runtime/vm/native_entry.cc
index ff7806260dc..7958cc107cb 100644
--- a/runtime/vm/native_entry.cc
+++ b/runtime/vm/native_entry.cc
@@ -119,7 +119,7 @@ extern "C" void DRT_BootstrapNativeCall(Dart_NativeArguments args,
 
 uword NativeEntry::BootstrapNativeCallWrapperEntry() {
   uword entry = reinterpret_cast<uword>(DRT_BootstrapNativeCall);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     entry = Simulator::RedirectExternalReference(
         entry, Simulator::kNativeCallWrapper,
@@ -165,7 +165,7 @@ extern "C" void DRT_NoScopeNativeCall(Dart_NativeArguments args,
 
 uword NativeEntry::NoScopeNativeCallWrapperEntry() {
   uword entry = reinterpret_cast<uword>(DRT_NoScopeNativeCall);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     entry = Simulator::RedirectExternalReference(
         entry, Simulator::kNativeCallWrapper,
@@ -198,7 +198,7 @@ extern "C" void DRT_AutoScopeNativeCall(Dart_NativeArguments args,
 
 uword NativeEntry::AutoScopeNativeCallWrapperEntry() {
   uword entry = reinterpret_cast<uword>(DRT_AutoScopeNativeCall);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     entry = Simulator::RedirectExternalReference(
         entry, Simulator::kNativeCallWrapper,
diff --git a/runtime/vm/object.cc b/runtime/vm/object.cc
index 299811b6b8d..c27c12ba0f4 100644
--- a/runtime/vm/object.cc
+++ b/runtime/vm/object.cc
@@ -27010,7 +27010,7 @@ const char* StackTrace::ToCString() const {
 #else
     const char kCompressedPointers[] = "no";
 #endif
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
     const char kUsingSimulator[] = "yes";
 #else
     const char kUsingSimulator[] = "no";
diff --git a/runtime/vm/object_test.cc b/runtime/vm/object_test.cc
index 97b5ee6c998..e5b294079e9 100644
--- a/runtime/vm/object_test.cc
+++ b/runtime/vm/object_test.cc
@@ -8206,7 +8206,8 @@ TEST_CASE(TypeArguments_Cache_SomeInstantiations) {
 // reasons. Any core issues will likely be found by SomeInstantiations.
 #if !defined(DEBUG) && !defined(USING_MEMORY_SANITIZER) &&                     \
     !defined(USING_THREAD_SANITIZER) && !defined(USING_LEAK_SANITIZER) &&      \
-    !defined(USING_UNDEFINED_BEHAVIOR_SANITIZER) && !defined(USING_SIMULATOR)
+    !defined(USING_UNDEFINED_BEHAVIOR_SANITIZER) &&                            \
+    !defined(DART_INCLUDE_SIMULATOR)
 TEST_CASE(TypeArguments_Cache_ManyInstantiations) {
   const intptr_t kNumClasses = 100000;
   static_assert(kNumClasses > TypeArguments::Cache::kMaxLinearCacheEntries,
diff --git a/runtime/vm/profiler.cc b/runtime/vm/profiler.cc
index cc9c00be632..07910217e06 100644
--- a/runtime/vm/profiler.cc
+++ b/runtime/vm/profiler.cc
@@ -45,7 +45,7 @@ DEFINE_FLAG(int,
             max_profile_depth,
             Sample::kPCArraySizeInWords* kMaxSamplesPerTick,
             "Maximum number stack frames walked. Minimum 1. Maximum 255.");
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 DEFINE_FLAG(bool, profile_vm, true, "Always collect native stack traces.");
 #else
 DEFINE_FLAG(bool, profile_vm, false, "Always collect native stack traces.");
@@ -363,7 +363,7 @@ static bool GetAndValidateThreadStackBounds(OSThread* os_thread,
   ASSERT(stack_lower != nullptr);
   ASSERT(stack_upper != nullptr);
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   const bool use_simulator_stack_bounds =
       FLAG_use_simulator && thread != nullptr && thread->IsExecutingDartCode();
   if (use_simulator_stack_bounds) {
@@ -375,7 +375,7 @@ static bool GetAndValidateThreadStackBounds(OSThread* os_thread,
   }
 #else
   const bool use_simulator_stack_bounds = false;
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 
   if (!use_simulator_stack_bounds) {
     *stack_lower = os_thread->stack_limit();
@@ -514,7 +514,7 @@ void Profiler::DumpStackTrace(uword sp, uword fp, uword pc, bool for_crash) {
 #else
   const char kCompressedPointers[] = "no";
 #endif
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   const char kUsingSimulator[] = "yes";
 #else
   const char kUsingSimulator[] = "no";
@@ -1249,7 +1249,7 @@ static Sample* SetupSample(Thread* thread,
   }
   sample->Init(isolate->main_port(), OS::GetCurrentMonotonicMicros(), tid);
   uword vm_tag = thread->vm_tag();
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   // When running in the simulator, the runtime entry function address
   // (stored as the vm tag) is the address of a redirect function.
   // Attempt to find the real runtime entry function address and use that.
@@ -1393,7 +1393,7 @@ void Profiler::SampleThread(Thread* thread,
 
   if (in_dart_code) {
     // If we're in Dart code, use the Dart stack pointer.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
     if (FLAG_use_simulator) {
       Simulator* simulator = isolate->simulator();
       sp = simulator->get_register(SPREG);
diff --git a/runtime/vm/runtime_entry.cc b/runtime/vm/runtime_entry.cc
index 88cf9098803..cd79ef62dff 100644
--- a/runtime/vm/runtime_entry.cc
+++ b/runtime/vm/runtime_entry.cc
@@ -123,7 +123,7 @@ uword RuntimeEntry::GetEntryPoint() const {
   // this is a redirection address that forces the simulator to call
   // into the runtime system.
   uword entry = reinterpret_cast<uword>(function());
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     // Redirection to leaf runtime calls supports a maximum of 4 arguments
     // passed in registers (maximum 2 double arguments for leaf float runtime
@@ -153,14 +153,14 @@ uword RuntimeEntry::GetEntryPoint() const {
   } while (0)
 #endif
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 #define CHECK_SIMULATOR_STACK_OVERFLOW()                                       \
   if (FLAG_use_simulator && !OSThread::Current()->HasStackHeadroom()) {        \
     Exceptions::ThrowStackOverflow();                                          \
   }
 #else
 #define CHECK_SIMULATOR_STACK_OVERFLOW()
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 
 void OnEveryRuntimeEntryCall(Thread* thread,
                              const char* runtime_call_name,
@@ -3490,7 +3490,7 @@ static void HandleOSRRequest(Thread* thread) {
 
 DEFINE_RUNTIME_ENTRY(InterruptOrStackOverflow, 0) {
   uword stack_pos = OSThread::GetCurrentStackPointer();
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     stack_pos = Simulator::Current()->get_sp();
     // If simulator was never called it may return 0 as a value of SPREG.
@@ -4384,7 +4384,7 @@ extern "C" uword /*ObjectPtr*/ InterpretCall(uword /*FunctionPtr*/ function_in,
 uword RuntimeEntry::InterpretCallEntry() {
 #if defined(DART_DYNAMIC_MODULES)
   uword entry = reinterpret_cast<uword>(InterpretCall);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     entry = Simulator::RedirectExternalReference(
         entry, Simulator::kLeafRuntimeCall, 5);
diff --git a/runtime/vm/signal_handler_android.cc b/runtime/vm/signal_handler_android.cc
index e605d0104f5..02949bc8541 100644
--- a/runtime/vm/signal_handler_android.cc
+++ b/runtime/vm/signal_handler_android.cc
@@ -76,7 +76,7 @@ uintptr_t SignalHandler::GetCStackPointer(const mcontext_t& mcontext) {
 }
 
 uintptr_t SignalHandler::GetDartStackPointer(const mcontext_t& mcontext) {
-#if defined(TARGET_ARCH_ARM64) && !defined(USING_SIMULATOR)
+#if defined(TARGET_ARCH_ARM64) && !defined(DART_INCLUDE_SIMULATOR)
   return static_cast<uintptr_t>(mcontext.regs[SPREG]);
 #else
   return GetCStackPointer(mcontext);
diff --git a/runtime/vm/signal_handler_linux.cc b/runtime/vm/signal_handler_linux.cc
index 31c33d514ae..1078498d77a 100644
--- a/runtime/vm/signal_handler_linux.cc
+++ b/runtime/vm/signal_handler_linux.cc
@@ -82,7 +82,7 @@ uintptr_t SignalHandler::GetCStackPointer(const mcontext_t& mcontext) {
 }
 
 uintptr_t SignalHandler::GetDartStackPointer(const mcontext_t& mcontext) {
-#if defined(TARGET_ARCH_ARM64) && !defined(USING_SIMULATOR)
+#if defined(TARGET_ARCH_ARM64) && !defined(DART_INCLUDE_SIMULATOR)
   return static_cast<uintptr_t>(mcontext.regs[SPREG]);
 #else
   return GetCStackPointer(mcontext);
diff --git a/runtime/vm/signal_handler_macos.cc b/runtime/vm/signal_handler_macos.cc
index 962dae66936..c05f49a3656 100644
--- a/runtime/vm/signal_handler_macos.cc
+++ b/runtime/vm/signal_handler_macos.cc
@@ -65,7 +65,7 @@ uintptr_t SignalHandler::GetCStackPointer(const mcontext_t& mcontext) {
 }
 
 uintptr_t SignalHandler::GetDartStackPointer(const mcontext_t& mcontext) {
-#if defined(TARGET_ARCH_ARM64) && !defined(USING_SIMULATOR)
+#if defined(TARGET_ARCH_ARM64) && !defined(DART_INCLUDE_SIMULATOR)
   return static_cast<uintptr_t>(mcontext->__ss.__x[SPREG]);
 #else
   return GetCStackPointer(mcontext);
diff --git a/runtime/vm/simulator.h b/runtime/vm/simulator.h
index 659bc8b2482..0b8c8cc294b 100644
--- a/runtime/vm/simulator.h
+++ b/runtime/vm/simulator.h
@@ -7,7 +7,7 @@
 
 #include "vm/globals.h"
 
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 #if defined(TARGET_ARCH_IA32)
 #error Simulator not implemented.
 #elif defined(TARGET_ARCH_X64)
@@ -21,6 +21,6 @@
 #else
 #error Unknown architecture.
 #endif  // defined(TARGET_ARCH_...)
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 
 #endif  // RUNTIME_VM_SIMULATOR_H_
diff --git a/runtime/vm/simulator_arm.cc b/runtime/vm/simulator_arm.cc
index a678ac23ad2..97cab5f9d22 100644
--- a/runtime/vm/simulator_arm.cc
+++ b/runtime/vm/simulator_arm.cc
@@ -9,7 +9,7 @@
 #if defined(TARGET_ARCH_ARM)
 
 // Only build the simulator if not compiling for real ARM hardware.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 
 #include "vm/simulator.h"
 
@@ -3710,6 +3710,6 @@ void Simulator::JumpToFrame(uword pc, uword sp, uword fp, Thread* thread) {
 
 }  // namespace dart
 
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 
 #endif  // defined TARGET_ARCH_ARM
diff --git a/runtime/vm/simulator_arm64.cc b/runtime/vm/simulator_arm64.cc
index 4c12e243ec7..4423b73d36d 100644
--- a/runtime/vm/simulator_arm64.cc
+++ b/runtime/vm/simulator_arm64.cc
@@ -9,7 +9,7 @@
 #if defined(TARGET_ARCH_ARM64)
 
 // Only build the simulator if not compiling for real ARM hardware.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 
 #include "vm/simulator.h"
 
@@ -4125,6 +4125,6 @@ void Simulator::JumpToFrame(uword pc, uword sp, uword fp, Thread* thread) {
 
 }  // namespace dart
 
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 #endif  // defined TARGET_ARCH_ARM64
diff --git a/runtime/vm/simulator_riscv.cc b/runtime/vm/simulator_riscv.cc
index b59e7a8382c..f716b472313 100644
--- a/runtime/vm/simulator_riscv.cc
+++ b/runtime/vm/simulator_riscv.cc
@@ -9,7 +9,7 @@
 #if defined(TARGET_ARCH_RISCV32) || defined(TARGET_ARCH_RISCV64)
 
 // Only build the simulator if not compiling for real RISCV hardware.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 
 #include "vm/simulator.h"
 
@@ -3451,6 +3451,6 @@ void Simulator::CSRClear(uint16_t csr, intx_t mask) {
 
 }  // namespace dart
 
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 #endif  // defined TARGET_ARCH_RISCV
diff --git a/runtime/vm/simulator_x64.cc b/runtime/vm/simulator_x64.cc
index 31b37921826..f5b1e0900e6 100644
--- a/runtime/vm/simulator_x64.cc
+++ b/runtime/vm/simulator_x64.cc
@@ -9,7 +9,7 @@
 #if defined(TARGET_ARCH_X64)
 
 // Only build the simulator if not compiling for real X64 hardware.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 
 #include "vm/simulator.h"
 
@@ -67,6 +67,6 @@ uword Simulator::FunctionForRedirect(uword redirect) {
 
 }  // namespace dart
 
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 
 #endif  // defined TARGET_ARCH_X64
diff --git a/runtime/vm/stack_frame.cc b/runtime/vm/stack_frame.cc
index 67df41cc801..030c46736aa 100644
--- a/runtime/vm/stack_frame.cc
+++ b/runtime/vm/stack_frame.cc
@@ -738,7 +738,7 @@ void StackFrameIterator::FrameSetIterator::Unpoison() {
   // instrumented C++, so there is nothing to unpoison. Additionally,
   // fp_ will be somewhere in the simulator's stack instead of the OSThread's
   // stack.
-#if !defined(USING_SIMULATOR)
+#if !defined(DART_INCLUDE_SIMULATOR)
   if (fp_ == 0) return;
   // Note that Thread::os_thread_ is cleared when the thread is descheduled.
   ASSERT(is_interpreted() || (thread_->os_thread() == nullptr) ||
@@ -754,7 +754,7 @@ void StackFrameIterator::FrameSetIterator::Unpoison() {
   uword upper = fp_ + kSavedCallerPcSlotFromFp * kWordSize;
   // Both lower and upper are inclusive, so we add one word when computing size.
   MSAN_UNPOISON(reinterpret_cast<void*>(lower), upper - lower + kWordSize);
-#endif  // !defined(USING_SIMULATOR)
+#endif  // !defined(DART_INCLUDE_SIMULATOR)
 }
 
 StackFrame* StackFrameIterator::FrameSetIterator::NextFrame(bool validate) {
diff --git a/runtime/vm/thread.cc b/runtime/vm/thread.cc
index 07c564641bb..1d5b2d7e872 100644
--- a/runtime/vm/thread.cc
+++ b/runtime/vm/thread.cc
@@ -532,7 +532,7 @@ void Thread::EnterIsolateGroupAsMutator(IsolateGroup* isolate_group,
   thread->SetupDartMutatorStateDependingOnSnapshot(isolate_group);
 
   ResumeThreadInternal(thread);
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   if (FLAG_use_simulator) {
     thread->SetStackLimit(Simulator::Current()->overflow_stack_limit());
   } else {
@@ -586,7 +586,7 @@ void Thread::ResumeDartMutatorThreadInternal(Thread* thread) {
   ResumeThreadInternal(thread);
   if (Dart::vm_isolate() != nullptr &&
       thread->isolate() != Dart::vm_isolate()) {
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
     if (FLAG_use_simulator) {
       thread->SetStackLimit(Simulator::Current()->overflow_stack_limit());
     } else {
@@ -1328,7 +1328,7 @@ intptr_t Thread::OffsetFromThread(const RuntimeEntry* runtime_entry) {
 bool Thread::TopErrorHandlerIsSetJump() const {
   if (long_jump_base() == nullptr) return false;
   if (top_exit_frame_info_ == 0) return true;
-#if defined(USING_SIMULATOR) || defined(USING_SAFE_STACK)
+#if defined(DART_INCLUDE_SIMULATOR) || defined(USING_SAFE_STACK)
   // False positives: simulator stack and native stack are unordered.
   return true;
 #else
@@ -1344,7 +1344,7 @@ bool Thread::TopErrorHandlerIsSetJump() const {
 bool Thread::TopErrorHandlerIsExitFrame() const {
   if (top_exit_frame_info_ == 0) return false;
   if (long_jump_base() == nullptr) return true;
-#if defined(USING_SIMULATOR) || defined(USING_SAFE_STACK)
+#if defined(DART_INCLUDE_SIMULATOR) || defined(USING_SAFE_STACK)
   // False positives: simulator stack and native stack are unordered.
   return true;
 #else
diff --git a/runtime/vm/thread_interrupter_macos.cc b/runtime/vm/thread_interrupter_macos.cc
index 0d07da01a09..5c7af4c21c7 100644
--- a/runtime/vm/thread_interrupter_macos.cc
+++ b/runtime/vm/thread_interrupter_macos.cc
@@ -114,7 +114,7 @@ class ThreadInterrupterMacOS {
     its.lr = state.__lr;
 #endif  // HOST_ARCH_...
 
-#if defined(TARGET_ARCH_ARM64) && !defined(USING_SIMULATOR)
+#if defined(TARGET_ARCH_ARM64) && !defined(DART_INCLUDE_SIMULATOR)
     its.dsp = state.__x[SPREG];
 #endif
     return its;
diff --git a/runtime/vm/thread_test.cc b/runtime/vm/thread_test.cc
index caba19be394..a3d50b4d7b6 100644
--- a/runtime/vm/thread_test.cc
+++ b/runtime/vm/thread_test.cc
@@ -624,11 +624,11 @@ TEST_CASE(SafepointTestDart) {
 // to get their verification done and exit. Use a specific UserTag
 // to enable the helpers to verify that the main thread is
 // successfully interrupted in the pure Dart loop.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
   const intptr_t kLoopCount = 12345678;
 #else
   const intptr_t kLoopCount = 1234567890;
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
   char buffer[1024];
   Utils::SNPrint(buffer, sizeof(buffer),
                  "import 'dart:developer';\n"
diff --git a/runtime/vm/unit_test.h b/runtime/vm/unit_test.h
index 9e2e948ff0e..0bfc10f5219 100644
--- a/runtime/vm/unit_test.h
+++ b/runtime/vm/unit_test.h
@@ -524,7 +524,7 @@ class AssemblerTest {
 // using the ABI calling convention.
 // ResultType is the return type of the assembler test function.
 // ArgNType is the type of the Nth argument.
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
 
   // Since Simulator::Call always return a int64_t, bit_cast does not work
   // on 32-bit platforms when returning an int32_t. Use static cast on the
@@ -611,7 +611,7 @@ class AssemblerTest {
     typedef ResultType (*FunctionType)(Arg1Type, Arg2Type, Arg3Type);
     return reinterpret_cast<FunctionType>(entry())(arg1, arg2, arg3);
   }
-#endif  // defined(USING_SIMULATOR)
+#endif  // defined(DART_INCLUDE_SIMULATOR)
 
   // Assemble test and set code_.
   void Assemble();
diff --git a/runtime/vm/version_in.cc b/runtime/vm/version_in.cc
index 7ff65c23c0c..c1106055fef 100644
--- a/runtime/vm/version_in.cc
+++ b/runtime/vm/version_in.cc
@@ -33,7 +33,7 @@ const char* Version::str_ =
     "{{VERSION_STR}} ({{CHANNEL}}) ({{COMMIT_TIME}})"
     " on \"" kHostOperatingSystemName
     "_"
-#if defined(USING_SIMULATOR)
+#if defined(DART_INCLUDE_SIMULATOR)
     "sim"
 #endif
     kTargetArchitectureName "\"";