diff --git a/packages/react-start/src/plugin/vite.ts b/packages/react-start/src/plugin/vite.ts
index 3d47aad887a..f6481cb73c7 100644
--- a/packages/react-start/src/plugin/vite.ts
+++ b/packages/react-start/src/plugin/vite.ts
@@ -45,10 +45,16 @@ export function tanstackStart(
                 : ['@tanstack/react-router', '@tanstack/react-router-devtools'],
           },
           optimizeDeps:
-            environmentName === VITE_ENVIRONMENT_NAMES.client ||
-            (environmentName === VITE_ENVIRONMENT_NAMES.server &&
-              // This indicates that the server environment has opted in to dependency optimization
-              options.optimizeDeps?.noDiscovery === false)
+            // Vitest uses Vite's config, but `optimizeDeps` (pre-bundling) causes conflicts
+            // when workspace packages (transformed by Vitest) interact with external packages (Node-native).
+            // This is especially problematic for React, leading to "Invalid hook call" errors due to
+            // duplicate React instances (one pre-bundled ESM, one native CJS).
+            // We disable this enforced optimization when running in Vitest to allow standard resolution.
+            process.env.VITEST !== 'true' &&
+            (environmentName === VITE_ENVIRONMENT_NAMES.client ||
+              (environmentName === VITE_ENVIRONMENT_NAMES.server &&
+                // This indicates that the server environment has opted in to dependency optimization
+                options.optimizeDeps?.noDiscovery === false))
               ? {
                   // As `@tanstack/react-start` depends on `@tanstack/react-router`, we should exclude both.
                   exclude: [