diff --git a/dev-packages/e2e-tests/test-applications/node-express-esm-loader/src/instrument.mjs b/dev-packages/e2e-tests/test-applications/node-express-esm-loader/src/instrument.mjs
index 544c773e5e7c..caaf73162ded 100644
--- a/dev-packages/e2e-tests/test-applications/node-express-esm-loader/src/instrument.mjs
+++ b/dev-packages/e2e-tests/test-applications/node-express-esm-loader/src/instrument.mjs
@@ -5,4 +5,5 @@ Sentry.init({
   dsn: process.env.E2E_TEST_DSN,
   tunnel: `http://localhost:3031/`, // proxy server
   tracesSampleRate: 1,
+  registerEsmLoaderHooks: { onlyIncludeInstrumentedModules: true },
 });
diff --git a/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/app.mjs b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/app.mjs
new file mode 100644
index 000000000000..6b20155aea38
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/app.mjs
@@ -0,0 +1,21 @@
+import { loggingTransport } from '@sentry-internal/node-integration-tests';
+import * as Sentry from '@sentry/node';
+import * as iitm from 'import-in-the-middle';
+
+new iitm.Hook((_, name) => {
+  if (name !== 'http') {
+    throw new Error(`'http' should be the only hooked modules but we just hooked '${name}'`);
+  }
+});
+
+Sentry.init({
+  dsn: 'https://public@dsn.ingest.sentry.io/1337',
+  release: '1.0',
+  autoSessionTracking: false,
+  transport: loggingTransport,
+  registerEsmLoaderHooks: { onlyIncludeInstrumentedModules: true },
+});
+
+await import('./sub-module.mjs');
+await import('http');
+await import('os');
diff --git a/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/sub-module.mjs b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/sub-module.mjs
new file mode 100644
index 000000000000..9940c57857eb
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/sub-module.mjs
@@ -0,0 +1,2 @@
+// eslint-disable-next-line no-console
+console.assert(true);
diff --git a/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/test.ts b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/test.ts
new file mode 100644
index 000000000000..8b9e6e06202f
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/esm/import-in-the-middle/test.ts
@@ -0,0 +1,12 @@
+import { conditionalTest } from '../../../utils';
+import { cleanupChildProcesses, createRunner } from '../../../utils/runner';
+
+afterAll(() => {
+  cleanupChildProcesses();
+});
+
+conditionalTest({ min: 18 })('import-in-the-middle', () => {
+  test('onlyIncludeInstrumentedModules', done => {
+    createRunner(__dirname, 'app.mjs').ensureNoErrorOutput().start(done);
+  });
+});
diff --git a/packages/node/src/sdk/initOtel.ts b/packages/node/src/sdk/initOtel.ts
index 03d8cea76fac..37b94ebc439f 100644
--- a/packages/node/src/sdk/initOtel.ts
+++ b/packages/node/src/sdk/initOtel.ts
@@ -10,6 +10,7 @@ import {
 import { SDK_VERSION } from '@sentry/core';
 import { SentryPropagator, SentrySampler, SentrySpanProcessor } from '@sentry/opentelemetry';
 import { GLOBAL_OBJ, consoleSandbox, logger } from '@sentry/utils';
+import { createAddHookMessageChannel } from 'import-in-the-middle';
 
 import { getOpenTelemetryInstrumentationToPreload } from '../integrations/tracing';
 import { SentryContextManager } from '../otel/contextManager';
@@ -31,6 +32,26 @@ export function initOpenTelemetry(client: NodeClient): void {
   client.traceProvider = provider;
 }
 
+type ImportInTheMiddleInitData = Pick<EsmLoaderHookOptions, 'include' | 'exclude'> & {
+  addHookMessagePort?: unknown;
+};
+
+interface RegisterOptions {
+  data?: ImportInTheMiddleInitData;
+  transferList?: unknown[];
+}
+
+function getRegisterOptions(esmHookConfig?: EsmLoaderHookOptions): RegisterOptions {
+  if (esmHookConfig?.onlyIncludeInstrumentedModules) {
+    const { addHookMessagePort } = createAddHookMessageChannel();
+    // If the user supplied include, we need to use that as a starting point or use an empty array to ensure no modules
+    // are wrapped if they are not hooked
+    return { data: { addHookMessagePort, include: esmHookConfig.include || [] }, transferList: [addHookMessagePort] };
+  }
+
+  return { data: esmHookConfig };
+}
+
 /** Initialize the ESM loader. */
 export function maybeInitializeEsmLoader(esmHookConfig?: EsmLoaderHookOptions): void {
   const [nodeMajor = 0, nodeMinor = 0] = process.versions.node.split('.').map(Number);
@@ -44,7 +65,7 @@ export function maybeInitializeEsmLoader(esmHookConfig?: EsmLoaderHookOptions):
     if (!GLOBAL_OBJ._sentryEsmLoaderHookRegistered && importMetaUrl) {
       try {
         // @ts-expect-error register is available in these versions
-        moduleModule.register('import-in-the-middle/hook.mjs', importMetaUrl, { data: esmHookConfig });
+        moduleModule.register('import-in-the-middle/hook.mjs', importMetaUrl, getRegisterOptions(esmHookConfig));
         GLOBAL_OBJ._sentryEsmLoaderHookRegistered = true;
       } catch (error) {
         logger.warn('Failed to register ESM hook', error);
diff --git a/packages/node/src/types.ts b/packages/node/src/types.ts
index 9604b31ddb22..aa9873e2da91 100644
--- a/packages/node/src/types.ts
+++ b/packages/node/src/types.ts
@@ -6,7 +6,18 @@ import type { NodeTransportOptions } from './transports';
 
 export interface EsmLoaderHookOptions {
   include?: Array<string | RegExp>;
-  exclude?: Array<string | RegExp>;
+  exclude?: Array<string | RegExp> /**
+   * When set to `true`, `import-in-the-middle` will only wrap ESM modules that are specifically instrumented by
+   * OpenTelemetry plugins. This is useful to avoid issues where `import-in-the-middle` is not compatible with some of
+   * your dependencies.
+   *
+   * **Note**: This feature will only work if you `Sentry.init()` the SDK before the instrumented modules are loaded.
+   * This can be achieved via the Node `--import` CLI flag or by loading your app via async `import()` after calling
+   * `Sentry.init()`.
+   *
+   * Defaults to `false`.
+   */;
+  onlyIncludeInstrumentedModules?: boolean;
 }
 
 export interface BaseNodeOptions {