--- a/dev-lang/python/python-3.8.8.ebuild	
+++ a/dev-lang/python/python-3.8.8.ebuild	
@@ -145,6 +145,11 @@ src_configure() {
 	# Fix implicit declarations on cross and prefix builds. Bug #674070.
 	use ncurses && append-cppflags -I"${ESYSROOT}"/usr/include/ncursesw
 
+	if [ -n "${ESYSROOT}" ]; then
+		append-cflags --sysroot="${ESYSROOT}"
+		append-ldflags --sysroot="${ESYSROOT}"
+	fi
+
 	local dbmliborder
 	if use gdbm; then
 		dbmliborder+="${dbmliborder:+:}gdbm"