diff --git a/packages/vite/src/node/__tests__/plugins/define.spec.ts b/packages/vite/src/node/__tests__/plugins/define.spec.ts
index 8876a9d7ecc3e2..2165461c77acaa 100644
--- a/packages/vite/src/node/__tests__/plugins/define.spec.ts
+++ b/packages/vite/src/node/__tests__/plugins/define.spec.ts
@@ -64,6 +64,20 @@ describe('definePlugin', () => {
     )
   })
 
+  test('replace import.meta.env.UNKNOWN with undefined', async () => {
+    const transform = await createDefinePluginTransform()
+    expect(await transform('const foo = import.meta.env.UNKNOWN;')).toBe(
+      'const foo = undefined                       ;\n',
+    )
+  })
+
+  test('leave import.meta.env["UNKNOWN"] to runtime', async () => {
+    const transform = await createDefinePluginTransform()
+    expect(await transform('const foo = import.meta.env["UNKNOWN"];')).toMatch(
+      /const __vite_import_meta_env__ = .*;\nconst foo = __vite_import_meta_env__\["UNKNOWN"\];/,
+    )
+  })
+
   test('preserve import.meta.env.UNKNOWN with override', async () => {
     const transform = await createDefinePluginTransform({
       'import.meta.env.UNKNOWN': 'import.meta.env.UNKNOWN',
@@ -72,4 +86,27 @@ describe('definePlugin', () => {
       'const foo = import.meta.env.UNKNOWN;\n',
     )
   })
+
+  test('replace import.meta.env when it is a invalid json', async () => {
+    const transform = await createDefinePluginTransform({
+      'import.meta.env.LEGACY': '__VITE_IS_LEGACY__',
+    })
+
+    expect(
+      await transform(
+        'const isLegacy = import.meta.env.LEGACY;\nimport.meta.env.UNDEFINED && console.log(import.meta.env.UNDEFINED);',
+      ),
+    ).toMatchInlineSnapshot(`
+      "const isLegacy = __VITE_IS_LEGACY__;
+      undefined                          && console.log(undefined                         );
+      "
+    `)
+  })
+
+  test('replace bare import.meta.env', async () => {
+    const transform = await createDefinePluginTransform()
+    expect(await transform('const env = import.meta.env;')).toMatch(
+      /const __vite_import_meta_env__ = .*;\nconst env = __vite_import_meta_env__;/,
+    )
+  })
 })
diff --git a/packages/vite/src/node/plugins/define.ts b/packages/vite/src/node/plugins/define.ts
index da50836294a0af..585bc0154fa263 100644
--- a/packages/vite/src/node/plugins/define.ts
+++ b/packages/vite/src/node/plugins/define.ts
@@ -2,12 +2,15 @@ import { transform } from 'esbuild'
 import { TraceMap, decodedMap, encodedMap } from '@jridgewell/trace-mapping'
 import type { ResolvedConfig } from '../config'
 import type { Plugin } from '../plugin'
-import { escapeRegex, getHash } from '../utils'
+import { escapeRegex } from '../utils'
 import { isCSSRequest } from './css'
 import { isHTMLRequest } from './html'
 
 const nonJsRe = /\.json(?:$|\?)/
 const isNonJsRequest = (request: string): boolean => nonJsRe.test(request)
+const importMetaEnvMarker = '__vite_import_meta_env__'
+const bareImportMetaEnvRe = new RegExp(`${importMetaEnvMarker}(?!\\.)\\b`)
+const importMetaEnvKeyRe = new RegExp(`${importMetaEnvMarker}\\..+?\\b`, 'g')
 
 export function definePlugin(config: ResolvedConfig): Plugin {
   const isBuild = config.command === 'build'
@@ -69,13 +72,16 @@ export function definePlugin(config: ResolvedConfig): Plugin {
       define['import.meta.env.SSR'] = ssr + ''
     }
     if ('import.meta.env' in define) {
-      define['import.meta.env'] = serializeDefine({
-        ...importMetaEnvKeys,
-        SSR: ssr + '',
-        ...userDefineEnv,
-      })
+      define['import.meta.env'] = importMetaEnvMarker
     }
 
+    const importMetaEnvVal = serializeDefine({
+      ...importMetaEnvKeys,
+      SSR: ssr + '',
+      ...userDefineEnv,
+    })
+    const banner = `const ${importMetaEnvMarker} = ${importMetaEnvVal};\n`
+
     // Create regex pattern as a fast check before running esbuild
     const patternKeys = Object.keys(userDefine)
     if (replaceProcessEnv && Object.keys(processEnv).length) {
@@ -88,7 +94,7 @@ export function definePlugin(config: ResolvedConfig): Plugin {
       ? new RegExp(patternKeys.map(escapeRegex).join('|'))
       : null
 
-    return [define, pattern] as const
+    return [define, pattern, banner] as const
   }
 
   const defaultPattern = generatePattern(false)
@@ -116,14 +122,32 @@ export function definePlugin(config: ResolvedConfig): Plugin {
         return
       }
 
-      const [define, pattern] = ssr ? ssrPattern : defaultPattern
+      const [define, pattern, banner] = ssr ? ssrPattern : defaultPattern
       if (!pattern) return
 
       // Check if our code needs any replacements before running esbuild
       pattern.lastIndex = 0
       if (!pattern.test(code)) return
 
-      return await replaceDefine(code, id, define, config)
+      const result = await replaceDefine(code, id, define, config)
+
+      // Replace `import.meta.env.*` with undefined
+      result.code = result.code.replaceAll(importMetaEnvKeyRe, (m) =>
+        'undefined'.padEnd(m.length),
+      )
+
+      // If there's bare `import.meta.env` references, prepend the banner
+      if (bareImportMetaEnvRe.test(result.code)) {
+        result.code = banner + result.code
+
+        if (result.map) {
+          const map = JSON.parse(result.map)
+          map.mappings = ';' + map.mappings
+          result.map = map
+        }
+      }
+
+      return result
     },
   }
 }
@@ -134,19 +158,6 @@ export async function replaceDefine(
   define: Record<string, string>,
   config: ResolvedConfig,
 ): Promise<{ code: string; map: string | null }> {
-  // Because esbuild only allows JSON-serializable values, and `import.meta.env`
-  // may contain values with raw identifiers, making it non-JSON-serializable,
-  // we replace it with a temporary marker and then replace it back after to
-  // workaround it. This means that esbuild is unable to optimize the `import.meta.env`
-  // access, but that's a tradeoff for now.
-  const replacementMarkers: Record<string, string> = {}
-  const env = define['import.meta.env']
-  if (env && !canJsonParse(env)) {
-    const marker = `_${getHash(env, env.length - 2)}_`
-    replacementMarkers[marker] = env
-    define = { ...define, 'import.meta.env': marker }
-  }
-
   const esbuildOptions = config.esbuild || {}
 
   const result = await transform(code, {
@@ -178,10 +189,6 @@ export async function replaceDefine(
     }
   }
 
-  for (const marker in replacementMarkers) {
-    result.code = result.code.replaceAll(marker, replacementMarkers[marker])
-  }
-
   return {
     code: result.code,
     map: result.map || null,
@@ -212,12 +219,3 @@ function handleDefineValue(value: any): string {
   if (typeof value === 'string') return value
   return JSON.stringify(value)
 }
-
-function canJsonParse(value: any): boolean {
-  try {
-    JSON.parse(value)
-    return true
-  } catch {
-    return false
-  }
-}
diff --git a/playground/define/__tests__/define.spec.ts b/playground/define/__tests__/define.spec.ts
index ec1801c7876ca4..399e9c801266a9 100644
--- a/playground/define/__tests__/define.spec.ts
+++ b/playground/define/__tests__/define.spec.ts
@@ -92,3 +92,16 @@ test('replaces constants in template literal expressions', async () => {
     ),
   ).toBe('dev')
 })
+
+test('replace constants on import.meta.env when it is a invalid json', async () => {
+  expect(
+    await page.textContent(
+      '.replace-undefined-constants-on-import-meta-env .import-meta-env-UNDEFINED',
+    ),
+  ).toBe('undefined')
+  expect(
+    await page.textContent(
+      '.replace-undefined-constants-on-import-meta-env .import-meta-env-SOME_IDENTIFIER',
+    ),
+  ).toBe('true')
+})
diff --git a/playground/define/index.html b/playground/define/index.html
index 2c2898771e5d4e..164ba46c64bd0e 100644
--- a/playground/define/index.html
+++ b/playground/define/index.html
@@ -60,6 +60,21 @@ <h2>Define replaces constants in template literal expressions</h2>
   <p>import.meta.hot <code class="import-meta-hot"></code></p>
 </section>
 
+<h2>Define undefined constants on import.meta.env when it's a invalid json</h2>
+<section class="replace-undefined-constants-on-import-meta-env">
+  <p>
+    import.meta.env.UNDEFINED <code class="import-meta-env-UNDEFINED"></code>
+  </p>
+  <p>
+    import.meta.env.SOME_IDENTIFIER
+    <code class="import-meta-env-SOME_IDENTIFIER"></code>
+  </p>
+</section>
+
+<script>
+  // inject __VITE_SOME_IDENTIFIER__ to test if it's replaced
+  window.__VITE_SOME_IDENTIFIER__ = true
+</script>
 <script type="module">
   const __VAR_NAME__ = true // ensure define doesn't replace var name
   text('.exp', typeof __EXP__) // typeof __EXP__ would be `boolean` instead of `string`
@@ -127,6 +142,15 @@ <h2>Define replaces constants in template literal expressions</h2>
     '.replaces-constants-in-template-literal-expressions .process-env-NODE_ENV',
     `${process.env.NODE_ENV}`,
   )
+
+  text(
+    '.replace-undefined-constants-on-import-meta-env .import-meta-env-UNDEFINED',
+    `${import.meta.env.UNDEFINED}`,
+  )
+  text(
+    '.replace-undefined-constants-on-import-meta-env .import-meta-env-SOME_IDENTIFIER',
+    `${import.meta.env.SOME_IDENTIFIER}`,
+  )
 </script>
 
 <style>
diff --git a/playground/define/vite.config.js b/playground/define/vite.config.js
index 997f2b9ae83931..d6c4d22709266b 100644
--- a/playground/define/vite.config.js
+++ b/playground/define/vite.config.js
@@ -29,5 +29,6 @@ export default defineConfig({
     ÖUNICODE_LETTERɵ: 789,
     __VAR_NAME__: false,
     __STRINGIFIED_OBJ__: JSON.stringify({ foo: true }),
+    'import.meta.env.SOME_IDENTIFIER': '__VITE_SOME_IDENTIFIER__',
   },
 })