diff --git a/pkgs/build-support/cc-wrapper/default.nix b/pkgs/build-support/cc-wrapper/default.nix
index 2a88e3369a99..345aaa71cf78 100644
--- a/pkgs/build-support/cc-wrapper/default.nix
+++ b/pkgs/build-support/cc-wrapper/default.nix
@@ -363,6 +363,22 @@ let
     else
       targetPlatform.darwinPlatform
   );
+
+  # Header files that use `__FILE__` (e.g., for error reporting) lead
+  # to unwanted references to development packages and outputs in built
+  # binaries, like C++ programs depending on GCC and Boost at runtime.
+  #
+  # We use `-fmacro-prefix-map` to avoid the store references in these
+  # situations while keeping them in compiler diagnostics and debugging
+  # and profiling output.
+  #
+  # Unfortunately, doing this with GCC runs into issues with compiler
+  # argument length limits due to <https://gcc.gnu.org/PR111527>, so we
+  # disable it there in favour of our existing patch.
+  #
+  # TODO: Drop `mangle-NIX_STORE-in-__FILE__.patch` from GCC and make
+  # this unconditional once the upstream bug is fixed.
+  useMacroPrefixMap = !isGNU;
 in
 
 assert includeFortifyHeaders' -> fortify-headers != null;
@@ -455,6 +471,14 @@ stdenvNoCC.mkDerivation {
       substituteAll "$wrapper" "$out/bin/$dst"
       chmod +x "$out/bin/$dst"
     }
+
+    include() {
+      printf -- '%s %s\n' "$1" "$2"
+      ${lib.optionalString useMacroPrefixMap ''
+        local scrubbed="$NIX_STORE/eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee-''${2#"$NIX_STORE"/*-}"
+        printf -- '-fmacro-prefix-map=%s=%s\n' "$2" "$scrubbed"
+      ''}
+    }
   ''
 
   + (
@@ -673,13 +697,13 @@ stdenvNoCC.mkDerivation {
         echo "-B${libc_lib}${libc.libdir or "/lib/"}" >> $out/nix-support/libc-crt1-cflags
       ''
       + optionalString (!(cc.langD or false)) ''
-        echo "-${
+        include "-${
           if isArocc then "I" else "idirafter"
-        } ${libc_dev}${libc.incdir or "/include"}" >> $out/nix-support/libc-cflags
+        }" "${libc_dev}${libc.incdir or "/include"}" >> $out/nix-support/libc-cflags
       ''
       + optionalString (isGNU && (!(cc.langD or false))) ''
         for dir in "${cc}"/lib/gcc/*/*/include-fixed; do
-          echo '-idirafter' ''${dir} >> $out/nix-support/libc-cflags
+          include '-idirafter' ''${dir} >> $out/nix-support/libc-cflags
         done
       ''
       + ''
@@ -695,7 +719,7 @@ stdenvNoCC.mkDerivation {
       # like option that forces the libc headers before all -idirafter,
       # hence -isystem here.
       + optionalString includeFortifyHeaders' ''
-        echo "-isystem ${fortify-headers}/include" >> $out/nix-support/libc-cflags
+        include -isystem "${fortify-headers}/include" >> $out/nix-support/libc-cflags
       ''
     )
 
@@ -718,19 +742,19 @@ stdenvNoCC.mkDerivation {
     # https://github.com/NixOS/nixpkgs/pull/209870#issuecomment-1500550903)
     + optionalString (libcxx == null && isClang && (useGccForLibs && gccForLibs.langCC or false)) ''
       for dir in ${gccForLibs}/include/c++/*; do
-        echo "-isystem $dir" >> $out/nix-support/libcxx-cxxflags
+        include -isystem "$dir" >> $out/nix-support/libcxx-cxxflags
       done
       for dir in ${gccForLibs}/include/c++/*/${targetPlatform.config}; do
-        echo "-isystem $dir" >> $out/nix-support/libcxx-cxxflags
+        include -isystem "$dir" >> $out/nix-support/libcxx-cxxflags
       done
     ''
     + optionalString (libcxx.isLLVM or false) ''
-      echo "-isystem ${getDev libcxx}/include/c++/v1" >> $out/nix-support/libcxx-cxxflags
+      include -isystem "${getDev libcxx}/include/c++/v1" >> $out/nix-support/libcxx-cxxflags
       echo "-stdlib=libc++" >> $out/nix-support/libcxx-ldflags
     ''
     # GCC NG friendly libc++
     + optionalString (libcxx != null && libcxx.isGNU or false) ''
-      echo "-isystem ${getDev libcxx}/include" >> $out/nix-support/libcxx-cxxflags
+      include -isystem "${getDev libcxx}/include" >> $out/nix-support/libcxx-cxxflags
     ''
 
     ##
@@ -937,6 +961,7 @@ stdenvNoCC.mkDerivation {
     inherit libc_bin libc_dev libc_lib;
     inherit darwinPlatformForCC;
     default_hardening_flags_str = builtins.toString defaultHardeningFlags;
+    inherit useMacroPrefixMap;
   }
   // lib.mapAttrs (_: lib.optionalString targetPlatform.isDarwin) {
     # These will become empty strings when not targeting Darwin.
diff --git a/pkgs/build-support/cc-wrapper/setup-hook.sh b/pkgs/build-support/cc-wrapper/setup-hook.sh
index 33a2b62a49b0..1c8b26061b03 100644
--- a/pkgs/build-support/cc-wrapper/setup-hook.sh
+++ b/pkgs/build-support/cc-wrapper/setup-hook.sh
@@ -68,12 +68,21 @@ ccWrapper_addCVars () {
     local role_post
     getHostRoleEnvHook
 
+    local found=
+
     if [ -d "$1/include" ]; then
         export NIX_CFLAGS_COMPILE${role_post}+=" -isystem $1/include"
+        found=1
     fi
 
     if [ -d "$1/Library/Frameworks" ]; then
         export NIX_CFLAGS_COMPILE${role_post}+=" -iframework $1/Library/Frameworks"
+        found=1
+    fi
+
+    if [[ -n "@useMacroPrefixMap@" && -n ${NIX_STORE:-} && -n $found ]]; then
+        local scrubbed="$NIX_STORE/eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee-${1#"$NIX_STORE"/*-}"
+        export NIX_CFLAGS_COMPILE${role_post}+=" -fmacro-prefix-map=$1=$scrubbed"
     fi
 }
 
diff --git a/pkgs/development/compilers/gcc/patches/default.nix b/pkgs/development/compilers/gcc/patches/default.nix
index 9a55332ade9b..dc6418c9241b 100644
--- a/pkgs/development/compilers/gcc/patches/default.nix
+++ b/pkgs/development/compilers/gcc/patches/default.nix
@@ -83,6 +83,10 @@ in
         # Do not try looking for binaries and libraries in /lib and /usr/lib
         ./13/no-sys-dirs-riscv.patch
         # Mangle the nix store hash in __FILE__ to prevent unneeded runtime references
+        #
+        # TODO: Remove these and the `useMacroPrefixMap` conditional
+        # in `cc-wrapper` once <https://gcc.gnu.org/PR111527>
+        # is fixed.
         ./13/mangle-NIX_STORE-in-__FILE__.patch
       ];
       "14" = [