diff --git a/packages/vite/src/node/__tests__/plugins/define.spec.ts b/packages/vite/src/node/__tests__/plugins/define.spec.ts
index 2ac85712b2a072..8876a9d7ecc3e2 100644
--- a/packages/vite/src/node/__tests__/plugins/define.spec.ts
+++ b/packages/vite/src/node/__tests__/plugins/define.spec.ts
@@ -32,6 +32,16 @@ describe('definePlugin', () => {
     )
   })
 
+  test('should not replace if not defined', async () => {
+    const transform = await createDefinePluginTransform({
+      __APP_VERSION__: JSON.stringify('1.0'),
+    })
+    expect(await transform('const version = "1.0";')).toBe(undefined)
+    expect(await transform('const version = import.meta.SOMETHING')).toBe(
+      undefined,
+    )
+  })
+
   test('replaces import.meta.env.SSR with false', async () => {
     const transform = await createDefinePluginTransform()
     expect(await transform('const isSSR = import.meta.env.SSR;')).toBe(
diff --git a/packages/vite/src/node/plugins/define.ts b/packages/vite/src/node/plugins/define.ts
index ccd6a5571a6e39..cce969843bfdde 100644
--- a/packages/vite/src/node/plugins/define.ts
+++ b/packages/vite/src/node/plugins/define.ts
@@ -83,18 +83,16 @@ export function definePlugin(config: ResolvedConfig): Plugin {
       })
     }
 
-    const defineKeys = Object.keys(define)
-    const pattern = defineKeys.length
-      ? new RegExp(
-          // Mustn't be preceded by a char that can be part of an identifier
-          // or a '.' that isn't part of a spread operator
-          '(?<![\\p{L}\\p{N}_$]|(?<!\\.\\.)\\.)(' +
-            defineKeys.map(escapeRegex).join('|') +
-            // Mustn't be followed by a char that can be part of an identifier
-            // or an assignment (but allow equality operators)
-            ')(?:(?<=\\.)|(?![\\p{L}\\p{N}_$]|\\s*?=[^=]))',
-          'gu',
-        )
+    // Create regex pattern as a fast check before running esbuild
+    const patternKeys = Object.keys(userDefine)
+    if (replaceProcessEnv && Object.keys(processEnv).length) {
+      patternKeys.push('process.env', '__vite_process_env_NODE_ENV')
+    }
+    if (Object.keys(importMetaKeys).length) {
+      patternKeys.push('import.meta.env', 'import.meta.hot')
+    }
+    const pattern = patternKeys.length
+      ? new RegExp(patternKeys.map(escapeRegex).join('|'))
       : null
 
     return [define, pattern] as const