diff --git a/3rdparty/wolfssl/CMakeLists.txt b/3rdparty/wolfssl/CMakeLists.txt
index 037628551b..e247b19854 100644
--- a/3rdparty/wolfssl/CMakeLists.txt
+++ b/3rdparty/wolfssl/CMakeLists.txt
@@ -27,18 +27,7 @@ else()
 
 	add_subdirectory(wolfssl EXCLUDE_FROM_ALL)
 
-	# TODO(cjj19970505@live.cn)
-	# This only works in single-config generator
-	# For a multi-config generator, we need to provide different wolfssl binaries for different config
-	if (GENERATOR_IS_MULTI_CONFIG)
-		message( FATAL_ERROR "RPCS3 can only be configured using single-config generator." )
-	endif()
-
-	if(MSVC)
-		set(WolfSSL_LIBRARY "${CMAKE_CURRENT_BINARY_DIR}/wolfssl/${CMAKE_BUILD_TYPE}/wolfssl.lib" CACHE INTERNAL "")
-	else()
-		set(WolfSSL_LIBRARY "${CMAKE_CURRENT_BINARY_DIR}/wolfssl/libwolfssl.a" CACHE INTERNAL "")
-	endif()
+	set(WolfSSL_LIBRARY "$<TARGET_FILE:wolfssl>" CACHE INTERNAL "")
 
 	# "${CMAKE_CURRENT_SOURCE_DIR}/wolfssl/wolfssl/" provides openssl headers
 	# So that curl can be built on an environment where openssl headers are not provided
diff --git a/rpcs3/Emu/System.cpp b/rpcs3/Emu/System.cpp
index 68a1554953..8158a481ea 100644
--- a/rpcs3/Emu/System.cpp
+++ b/rpcs3/Emu/System.cpp
@@ -41,7 +41,7 @@
 
 #include "display_sleep_control.h"
 
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 #include "Emu/RSX/VK/VulkanAPI.h"
 #endif
 
@@ -718,7 +718,7 @@ game_boot_result Emulator::Load(const std::string& title_id, bool add_only, bool
 		if (!add_only)
 		{
 			// Log some extra info in case of boot
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 			if (g_cfg.video.renderer == video_renderer::vulkan)
 			{
 				sys_log.notice("Vulkan SDK Revision: %d", VK_HEADER_VERSION);
diff --git a/rpcs3/emucore.vcxproj b/rpcs3/emucore.vcxproj
index f967666902..d3f4c2122a 100644
--- a/rpcs3/emucore.vcxproj
+++ b/rpcs3/emucore.vcxproj
@@ -42,6 +42,8 @@
       <PrecompiledHeader>Use</PrecompiledHeader>
       <AdditionalIncludeDirectories>..\3rdparty\wolfssl\wolfssl;..\3rdparty\flatbuffers\include;..\3rdparty\libusb\libusb\libusb;..\3rdparty\yaml-cpp\yaml-cpp\include;..\3rdparty\zlib\zlib;..\llvm\include;..\llvm_build\include;$(VULKAN_SDK)\Include</AdditionalIncludeDirectories>
       <Optimization Condition="'$(Configuration)|$(Platform)'=='Release|x64'">MaxSpeed</Optimization>
+      <PreprocessorDefinitions Condition="'$(Configuration)|$(Platform)'=='Debug|x64'">HAVE_VULKAN;%(PreprocessorDefinitions)</PreprocessorDefinitions>
+      <PreprocessorDefinitions Condition="'$(Configuration)|$(Platform)'=='Release|x64'">HAVE_VULKAN;%(PreprocessorDefinitions)</PreprocessorDefinitions>
     </ClCompile>
     <PreBuildEvent>
       <Command>cmd.exe /c "$(SolutionDir)\Utilities\git-version-gen.cmd"</Command>
diff --git a/rpcs3/headless_application.cpp b/rpcs3/headless_application.cpp
index 41c2e35e02..8424878d48 100644
--- a/rpcs3/headless_application.cpp
+++ b/rpcs3/headless_application.cpp
@@ -73,7 +73,7 @@ void headless_application::InitializeCallbacks()
 			break;
 		}
 		case video_renderer::opengl:
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 		case video_renderer::vulkan:
 #endif
 		{
diff --git a/rpcs3/main.cpp b/rpcs3/main.cpp
index f76c091dde..fa666e886d 100644
--- a/rpcs3/main.cpp
+++ b/rpcs3/main.cpp
@@ -26,6 +26,15 @@
 #ifdef _WIN32
 #include <windows.h>
 #include "util/dyn_lib.hpp"
+
+// TODO(cjj19970505@live.cn)
+// When compiling with WIN32_LEAN_AND_MEAN definition
+// NTSTATUS is defined in CMake build but not in VS build
+// May be caused by some different header pre-inclusion between CMake and VS configurations.
+#if !defined(NTSTATUS)
+// Copied from ntdef.h
+typedef _Return_type_success_(return >= 0) LONG NTSTATUS;
+#endif
 DYNAMIC_IMPORT("ntdll.dll", NtQueryTimerResolution, NTSTATUS(PULONG MinimumResolution, PULONG MaximumResolution, PULONG CurrentResolution));
 DYNAMIC_IMPORT("ntdll.dll", NtSetTimerResolution, NTSTATUS(ULONG DesiredResolution, BOOLEAN SetResolution, PULONG CurrentResolution));
 #else
diff --git a/rpcs3/rpcs3.vcxproj b/rpcs3/rpcs3.vcxproj
index 5040942f6c..dbbd6de098 100644
--- a/rpcs3/rpcs3.vcxproj
+++ b/rpcs3/rpcs3.vcxproj
@@ -79,7 +79,7 @@
       <DisableSpecificWarnings>4577;4467;%(DisableSpecificWarnings)</DisableSpecificWarnings>
       <ObjectFileName>$(IntDir)</ObjectFileName>
       <Optimization>MaxSpeed</Optimization>
-      <PreprocessorDefinitions>_WINDOWS;UNICODE;WIN32;WIN64;WITH_DISCORD_RPC;QT_NO_DEBUG;QT_WIDGETS_LIB;QT_GUI_LIB;QT_CORE_LIB;NDEBUG;QT_WINEXTRAS_LIB;QT_CONCURRENT_LIB;QT_MULTIMEDIA_LIB;QT_MULTIMEDIAWIDGETS_LIB;QT_SVG_LIB;%(PreprocessorDefinitions)</PreprocessorDefinitions>
+      <PreprocessorDefinitions>_WINDOWS;UNICODE;WIN32;WIN64;WIN32_LEAN_AND_MEAN;HAVE_VULKAN;WITH_DISCORD_RPC;QT_NO_DEBUG;QT_WIDGETS_LIB;QT_GUI_LIB;QT_CORE_LIB;NDEBUG;QT_WINEXTRAS_LIB;QT_CONCURRENT_LIB;QT_MULTIMEDIA_LIB;QT_MULTIMEDIAWIDGETS_LIB;QT_SVG_LIB;%(PreprocessorDefinitions)</PreprocessorDefinitions>
       <PreprocessToFile>false</PreprocessToFile>
       <ProgramDataBaseFileName>$(IntDir)vc$(PlatformToolsetVersion).pdb</ProgramDataBaseFileName>
       <RuntimeTypeInfo>true</RuntimeTypeInfo>
@@ -130,7 +130,7 @@
       <DisableSpecificWarnings>4577;4467;%(DisableSpecificWarnings)</DisableSpecificWarnings>
       <ObjectFileName>$(IntDir)</ObjectFileName>
       <Optimization>Disabled</Optimization>
-      <PreprocessorDefinitions>_WINDOWS;UNICODE;WIN32;WIN64;QT_WIDGETS_LIB;QT_GUI_LIB;QT_CORE_LIB;QT_WINEXTRAS_LIB;QT_CONCURRENT_LIB;QT_MULTIMEDIA_LIB;QT_MULTIMEDIAWIDGETS_LIB;QT_SVG_LIB;%(PreprocessorDefinitions)</PreprocessorDefinitions>
+      <PreprocessorDefinitions>_WINDOWS;UNICODE;WIN32;WIN64;WIN32_LEAN_AND_MEAN;HAVE_VULKAN;QT_WIDGETS_LIB;QT_GUI_LIB;QT_CORE_LIB;QT_WINEXTRAS_LIB;QT_CONCURRENT_LIB;QT_MULTIMEDIA_LIB;QT_MULTIMEDIAWIDGETS_LIB;QT_SVG_LIB;%(PreprocessorDefinitions)</PreprocessorDefinitions>
       <PreprocessToFile>false</PreprocessToFile>
       <RuntimeTypeInfo>true</RuntimeTypeInfo>
       <SuppressStartupBanner>true</SuppressStartupBanner>
diff --git a/rpcs3/rpcs3qt/CMakeLists.txt b/rpcs3/rpcs3qt/CMakeLists.txt
index de12f49031..1803d4c8e3 100644
--- a/rpcs3/rpcs3qt/CMakeLists.txt
+++ b/rpcs3/rpcs3qt/CMakeLists.txt
@@ -108,6 +108,12 @@ set_target_properties(rpcs3_ui
         AUTOUIC ON
         AUTORCC ON)
 
+# AUTOMOC brings Windows.h to the sources, which have some definitions conflicting with winsock2.h
+# define WIN32_LEAN_AND_MEAN resolve the problem
+# https://docs.microsoft.com/en-us/windows/win32/winsock/creating-a-basic-winsock-application
+# https://docs.microsoft.com/en-us/windows/win32/winprog/using-the-windows-headers#faster-builds-with-smaller-header-files
+target_compile_definitions(rpcs3_ui PRIVATE WIN32_LEAN_AND_MEAN)
+
 target_link_libraries(rpcs3_ui
     PUBLIC
         3rdparty::qt5 3rdparty::yaml-cpp
diff --git a/rpcs3/rpcs3qt/gui_application.cpp b/rpcs3/rpcs3qt/gui_application.cpp
index 5e65b09e7d..6568cbd708 100644
--- a/rpcs3/rpcs3qt/gui_application.cpp
+++ b/rpcs3/rpcs3qt/gui_application.cpp
@@ -1,8 +1,3 @@
-#ifdef _WIN32
-// This is to avoid inclusion of winsock.h from windows.h header which creates conflicts with inclusion of winsock2.h later
-#define _WINSOCKAPI_
-#endif
-
 #include "gui_application.h"
 
 #include "qt_utils.h"
@@ -46,7 +41,7 @@
 #include "Emu/RSX/Null/NullGSRender.h"
 #include "Emu/RSX/GL/GLGSRender.h"
 
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 #include "Emu/RSX/VK/VKGSRender.h"
 #endif
 
@@ -342,7 +337,7 @@ void gui_application::InitializeCallbacks()
 			g_fxo->init<rsx::thread, named_thread<GLGSRender>>();
 			break;
 		}
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 		case video_renderer::vulkan:
 		{
 			g_fxo->init<rsx::thread, named_thread<VKGSRender>>();
diff --git a/rpcs3/rpcs3qt/render_creator.cpp b/rpcs3/rpcs3qt/render_creator.cpp
index d03e94a929..1b9135dc57 100644
--- a/rpcs3/rpcs3qt/render_creator.cpp
+++ b/rpcs3/rpcs3qt/render_creator.cpp
@@ -4,7 +4,7 @@
 
 #include "Utilities/Thread.h"
 
-#if defined(_WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 #include "Emu/RSX/VK/vkutils/instance.hpp"
 #endif
 
@@ -20,7 +20,7 @@ constexpr auto qstr = QString::fromStdString;
 
 render_creator::render_creator(QObject *parent) : QObject(parent)
 {
-#if defined(WIN32) || defined(HAVE_VULKAN)
+#if defined(HAVE_VULKAN)
 	// Some drivers can get stuck when checking for vulkan-compatible gpus, f.ex. if they're waiting for one to get
 	// plugged in. This whole contraption is for showing an error message in case that happens, so that user has
 	// some idea about why the emulator window isn't showing up.