diff --git a/spring-boot-project/spring-boot/src/main/java/org/springframework/boot/context/config/ConfigDataEnvironmentContributor.java b/spring-boot-project/spring-boot/src/main/java/org/springframework/boot/context/config/ConfigDataEnvironmentContributor.java
index 4d74198c1e2..1822947978f 100644
--- a/spring-boot-project/spring-boot/src/main/java/org/springframework/boot/context/config/ConfigDataEnvironmentContributor.java
+++ b/spring-boot-project/spring-boot/src/main/java/org/springframework/boot/context/config/ConfigDataEnvironmentContributor.java
@@ -1,5 +1,5 @@
 /*
- * Copyright 2012-2024 the original author or authors.
+ * Copyright 2012-2025 the original author or authors.
  *
  * Licensed under the Apache License, Version 2.0 (the "License");
  * you may not use this file except in compliance with the License.
@@ -29,6 +29,7 @@ import java.util.stream.StreamSupport;
 import org.springframework.boot.context.properties.bind.Binder;
 import org.springframework.boot.context.properties.bind.PlaceholdersResolver;
 import org.springframework.boot.context.properties.source.ConfigurationPropertySource;
+import org.springframework.boot.origin.OriginLookup;
 import org.springframework.core.convert.ConversionService;
 import org.springframework.core.env.Environment;
 import org.springframework.core.env.PropertySource;
@@ -414,7 +415,7 @@ class ConfigDataEnvironmentContributor implements Iterable<ConfigDataEnvironment
 	static ConfigDataEnvironmentContributor ofExisting(PropertySource<?> propertySource,
 			ConversionService conversionService) {
 		return new ConfigDataEnvironmentContributor(Kind.EXISTING, null, null, false, propertySource,
-				ConfigurationPropertySource.from(propertySource), null, null, null, conversionService);
+				asConfigurationPropertySource(propertySource), null, null, null, conversionService);
 	}
 
 	/**
@@ -434,9 +435,16 @@ class ConfigDataEnvironmentContributor implements Iterable<ConfigDataEnvironment
 			ConversionService conversionService) {
 		PropertySource<?> propertySource = configData.getPropertySources().get(propertySourceIndex);
 		ConfigData.Options options = configData.getOptions(propertySource);
-		ConfigurationPropertySource configurationPropertySource = ConfigurationPropertySource.from(propertySource);
 		return new ConfigDataEnvironmentContributor(Kind.UNBOUND_IMPORT, location, resource, profileSpecific,
-				propertySource, configurationPropertySource, null, options, null, conversionService);
+				propertySource, asConfigurationPropertySource(propertySource), null, options, null, conversionService);
+	}
+
+	private static ConfigurationPropertySource asConfigurationPropertySource(PropertySource<?> propertySource) {
+		ConfigurationPropertySource configurationPropertySource = ConfigurationPropertySource.from(propertySource);
+		if (configurationPropertySource != null && propertySource instanceof OriginLookup<?> originLookup) {
+			configurationPropertySource = configurationPropertySource.withPrefix(originLookup.getPrefix());
+		}
+		return configurationPropertySource;
 	}
 
 	/**
diff --git a/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/TestApplicationEnvironment.java b/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/TestApplicationEnvironment.java
new file mode 100644
index 00000000000..62868352d32
--- /dev/null
+++ b/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/TestApplicationEnvironment.java
@@ -0,0 +1,26 @@
+/*
+ * Copyright 2012-2025 the original author or authors.
+ *
+ * Licensed under the Apache License, Version 2.0 (the "License");
+ * you may not use this file except in compliance with the License.
+ * You may obtain a copy of the License at
+ *
+ *      https://www.apache.org/licenses/LICENSE-2.0
+ *
+ * Unless required by applicable law or agreed to in writing, software
+ * distributed under the License is distributed on an "AS IS" BASIS,
+ * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+ * See the License for the specific language governing permissions and
+ * limitations under the License.
+ */
+
+package org.springframework.boot;
+
+/**
+ * Public version {@link ApplicationEnvironment} for tests to use.
+ *
+ * @author Phillip Webb
+ */
+public class TestApplicationEnvironment extends ApplicationEnvironment {
+
+}
diff --git a/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/context/config/ConfigDataEnvironmentPostProcessorIntegrationTests.java b/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/context/config/ConfigDataEnvironmentPostProcessorIntegrationTests.java
index 12005f44db1..0b1c19ba415 100644
--- a/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/context/config/ConfigDataEnvironmentPostProcessorIntegrationTests.java
+++ b/spring-boot-project/spring-boot/src/test/java/org/springframework/boot/context/config/ConfigDataEnvironmentPostProcessorIntegrationTests.java
@@ -38,6 +38,7 @@ import org.junit.jupiter.api.Test;
 import org.junit.jupiter.api.io.TempDir;
 
 import org.springframework.boot.SpringApplication;
+import org.springframework.boot.TestApplicationEnvironment;
 import org.springframework.boot.WebApplicationType;
 import org.springframework.boot.context.properties.bind.BindContext;
 import org.springframework.boot.context.properties.bind.BindException;
@@ -461,6 +462,21 @@ class ConfigDataEnvironmentPostProcessorIntegrationTests {
 		assertThat(context.getEnvironment().getProperty("my.property")).isEqualTo("fromotherpropertiesfile");
 	}
 
+	@Test // gh-45387
+	void runWhenProfileActivatedViaSystemEnvironmentVariableWithPrefix() {
+		this.application.setEnvironmentPrefix("example.prefix");
+		this.application.setEnvironment(new TestApplicationEnvironment() {
+
+			@Override
+			public Map<String, Object> getSystemEnvironment() {
+				return Map.of("EXAMPLE_PREFIX_SPRING_PROFILES_ACTIVE", "other,dev");
+			}
+
+		});
+		ConfigurableApplicationContext context = this.application.run();
+		assertThat(context.getEnvironment().getActiveProfiles()).contains("dev", "other");
+	}
+
 	@Test
 	@WithResource(name = "application.yaml", content = """
 			---