It is an old game. It was released when 60Hz was the standard and players were running their games on Windows 7 and were happy with 60fps. Hence it needs tweaking to run on new systems. Especially high refresh rates, the security and privacy features of Windows 10/11, High DPI Scaling, and OneDrive can cause problems.

1. Set "Windows 7"-compatibility. Go to Fallout 4's Steam folder, i.e.:
   
   C:\Program Files (x86)\Steam\steamapps\common\Fallout 4\
   
   and set both, Fallout4.exe and Fallout4Launcher.exe, to run in "Windows 7"-compatibility mode. Right-click each file, and see Properties->Compatibility->Compatibility mode. This helps with symptoms such as the game losing focus while starting in fullscreen mode, opening a window only to switch to fullscreen mode, or randomly minimising during gameplay. In the properties, one can further set these files to run as Administrator, although this is not recommended. It can help the game access files and devices (see note on OneDrive below).
   
   
2. Disable High DPI Scaling by setting the scale to 100% in the Windows settings System->Display->Scale, or by setting an override in the properties of the game's executable files under the Compatibility tab, Properties->Compatibility->Change high DPI settings. Set the High DPI setting override to "Application" for Fallout4.exe and Fallout4Launcher.exe.
   
   
3. Set your display's refresh rate to 60Hz, 120Hz or 180Hz, or limit the game's frame rate to 60fps in the graphics driver, using tools or mods. A display's refresh rate can be changed in the Windows Settings under System->Display->Advanced. A too high frame rate causes the game's physics to run too fast, dialogues to cut short, the player to get stuck at terminals, and black screens and crashes. Open the file Fallout4Prefs.ini in Documents\My Games\Fallout4\ and search for:
   
   [Display] ... iPresentInterval=0
   Set this value to 0 (null) to turn VSync off, for example when you want to enable VSync in the driver or limit the frame rate by other means. A value of 1 means to sync 1:1 with the refresh rate of a display, limiting the game to 60fps with a 60Hz display. A value of 2 means to sync 1:2 with the refresh rate, limiting the game to 60fps with a 120Hz display. A value of 3 means to sync 1:3 with the refresh rate, limiting the game to 60fps with a 180Hz display.
   
   Warning: iPresentInterval works as described for fullscreen mode, but for windowed mode is it bugged, and a value of 1 fails to sync with every refresh, and syncs with every second refresh instead. A value of 2 syncs with every third refresh, and a value of 3 syncs with every fourth refresh!! When you have a 60Hz display then switch to fullscreen mode.
   
   As an alternative and when you are familiar with modding can you use a mod to run the game at higher frame rates:
   High FPS Physics Fix - https://www.nexusmods.com/fallout4/mods/44798
   
   
4. If you have an Nvidia card then disable Weapon Debris in the game's launcher. See under the advanced options there. Nvidia has changed the API in recent times and weapon debris only works on older GTX cards. Newer GTX cards and RTX cards will cause a crash randomly early in the game.
   
   There, too, is a mod that will allow weapon debris to work on newer Nvidia cards:
   Weapon Debris Crash Fix - https://www.nexusmods.com/fallout4/mods/48078

• One can use Nvidia's GeForce Experience or NVIDIA App to optimise the game's settings for one's hardware. This will disable Weapon Debris, enable NVHBAO+ (Nvidia's ambient occlusion), allow for a range of settings from quality to performance, and let one set the desired resolution and display mode for the game. When DLDSR is enabled in the driver can one use DLDSR with Fallout 4 to get more detailed graphics. Similar optimisations are available with AMD's Adrenalin software for AMD graphics.
  
  
• Alternatively can one use Bilago's Configuration Tool to change the game's settings. It offers a graphical user interface to change settings such as the resolution and display mode, vsync, shadow quality, HUD colour, mouse sensitivity, controller support, and much more:
  Bilago's Configuration Tool - https://www.nexusmods.com/fallout4/mods/102
  
  
• If the game cannot create its .ini files and cannot save game files in the Documents folder, then check whether you have Controlled Folder Access in Windows enabled, and if so, add Fallout4.exe and Fallout4Launcher.exe to the list of allowed apps. Check your anti-virus software if you have any installed and create an exception for the game when it is blocking it. See Windows settings Privacy & Security->Windows Security->Virus & threat protection->Virus & threat protection settings->Manage settings->Controlled folder access as well as ->Exclusions.
  https://www.elevenforum.com/t/enable-or-disable-controlled-folder-access-for-microsoft-defender-antivirus-in-windows-11.4013/
  Further, check whether OneDrive is enabled and if necessary restore the Documents folder to its original location:
  https://www.elevenforum.com/t/move-or-restore-default-location-of-documents-folder-in-windows-11.8708/
  
  
• If keyboard&mouse are not working then unplug any controller, racing wheel, and joystick, reboot Windows, and try again. An advanced keyboard with an integrated controller and mousepad can confuse the game. Switch to a standard keyboard and mouse combination. Further check Fallout4Prefs.ini for:
  
  [General] ... bGamepadEnable=0
  Set this value to 0 (null) to disable controller support and to enable keyboard&mouse, or, to 1 to enable controller support and to disable keyboard&mouse.

• When dialogues are being cut off early or NPCs start talking over each other then the game's frame rate is likely too high. Limit it to 60fps or use a mod for high frame rates.
  
  
• If you have gaming audio software like SteelSeries or Razor, then check there first. The game can only do up to 6 channel audio (5.1 surround), and software with 8 channels, i.e. for 7.1 surround, can fail and needs tweaking.
  
  
• Audio devices with 24-bit sampling need to be switched to 16-bit when these cannot automatically resample older sound, i.e. 16-bit 44.1kHz or 16-bit 48kHz. See Windows settings System->Sound->Output (click the device)->Output settings->Format.
  Windows N editions, i.e. "Windows 11 Home N" (see Windows Settings->System->About) may need the Media Feature Pack by Microsoft installed because the N edition has excluded some audio codecs. This may also add resampling for 24-bit to/from 16-bit or 44.1kHz to 48kHz to devices that cannot handle this directly. See Microsoft:
  https://support.microsoft.com/en-gb/topic/media-feature-pack-list-for-windows-n-editions-c1c6fffa-d052-8338-7a79-a4bb980a700a
  
  
• Audio over HDMI can be limited due to older standards not supporting high bandwidths (i.e. HDMI 2.0 can handle at most 4K@60Hz) and the graphics driver being outdated. Use higher HDMI standards including the cable, use a lower resolution, update the graphics driver, or switch to on-board audio and other audio devices.
  
  
• Audio over HDMI and other connections can get suspended and after a resume introduce a delay in the audio stream. Try disabling the power management for the interface (USB, Bluetooth, ...) or avoid long durations of silence, i.e. by avoiding Alt-Tabbing out of the game for too long. To disable power management for an interface open Windows Settings->System->About->Related->Device Manager, find the interface to your audio device such as the USB or Bluetooth adapter, open Properties->Power Management and uncheck "Allow the computer to turn off this device to save power".
  
  
• Too quiet sound can be avoided by disabling Microsoft's audio enhancements. See Windows settings System->Sound->Output (click the device)->Audio enhancements.

• Update graphics drivers, avoid over-clocking, and check for over-heating.
  
• The game uses shaders for its graphics. These shaders are created at runtime and are stored in caches. These caches can become outdated or damaged. Clear the shader caches when you see graphical glitches.
  
  • Windows:
    AppData\Local\D3DSCache\
    
    
  • Steam:
    C:\Program Files (x86)\Steam\steamapps\shadercache\377160\
    
    
  • Nvidia: disable the shader cache in the Nvidia Control Panel, delete all files in the cache directories, and reenable the cache again:
    AppData\LocalLow\NVIDIA\PerDriverVersion\DXCache\
    AppData\Local\NVIDIA Corporation\NV_Cache\
    
    
  • AMD: reset the shader cache in the AMD Adrenalin settings, or delete the files in:
    AppData\Local\AMD\Dxcache\
    AppData\Local\AMD\DxcCache\

The game can crash to the desktop (CtD) for several reasons. These are some of them:

• Incomplete or damaged game files. Verify the game files in the Steam client.
  
• Outdated drivers and pending Windows updates. Update drivers and Windows.
  
• Installing a mod, or removing a mod mid-game. Read or watch a modding guide for more information.
  
• A broken or damaged savefile. Load an earlier savefile.
  
• A too high frame rate. Limit the frame rate to 60fps.
  
• Weapon debris is enabled on Nvidia cards. Disable it in the launcher settings.
  
• A bad or misspelled entry in the .ini file settings. Undo your changes, or, delete the .ini files and let the launcher create new ones.
  
• A bad resolution with High DPI Scaling enabled. Disable High DPI Scaling and select a new resolution in the launcher.
  
• Streaming- and video recording software, additional overlays, and background processes can interfere with the game. Disable them.
  
• Missing, outdated, or damaged system libraries. Reinstall DirectX 11, DotNet, and VisualC++ libraries.
  DirectX https://www.microsoft.com/en-gb/download/details.aspx?id=35
  DotNet https://dotnet.microsoft.com/en-us/download/dotnet-framework
  VisualC++ https://learn.microsoft.com/en-US/cpp/windows/latest-supported-vc-redist

• The interface is unpleasant, too stretched out, or has edges. Use a mod as an alternative:
  
  21:9 - https://www.nexusmods.com/fallout4/mods/65677
  32:9 - https://www.nexusmods.com/fallout4/mods/56363

• The game is installed on an old hard disk and cannot load its data fast enough. Install it on a fast SSD.
  
• The frame rate is below 60fps and the game's response is slow. Uninstall the High Texture Pack DLC when your graphics card cannot handle it well. Reduce graphics settings. Increase the frame rate by installing the "High FPS Physics Fix" mod.

• The game cannot access its .ini files and uses its default setting. It is often caused by anti-virus software, Windows' Controlled Folder Access, or OneDrive blocking the game's file access. Disable them or create exceptions for Fallout4.exe and Fallout4Launcher.exe.
  
• High DPI Scaling is enabled with a scale greater than 100%. Disable it or set overrides for the .exe files.

• The game opens minimised, likely due to a second display being connected previously. Check with LeftWinKey+Tab if the game is running on another display. Disable "Remember window locations" and "Minimise windows" in Windows settings System->Display->Multiple Displays.
  
• The game opens on the wrong screen. Use LeftWinKey+Shift+ArrowKeys to move it. See also Windows Settings->Display->Multiple Displays

• Loading is tied to the frame rate and can take up to several minutes. Alt-Tab to the desktop and back again speeds it up. Increase the game's frame rates. Install a load accelerator mod such as the "High FPS Physics Fix" (see Too Low or Too High Frame Rates below).

• The game is stuck in a long loading sequence. See above.
  
• The game runs at a too high frame rate, which breaks the loading sequence. Limit the frame rate to 60fps. Install the "High FPS Physics Fix" mod.
  
• The game is stuck creating an autosave file. Disable autosave. Check disk space. Disable OneDrive.
  
• The .ini files contain a bad value. Undo your changes, or, delete the .ini files and let the launcher create new ones.

• The game produces low frame rates. Set it to run on a dedicated gaming GPU and avoid using any integrated GPU.
  
  
• The game produces low frame rates when the laptop runs on battery. The laptop may be using the integrated GPU to conserve power. Plug the laptop into an outlet or switch to a dedicated gaming GPU when running on battery.
  
  
• The game produces low frame rates. (Re-)Enable fullscreen and windowed optimisations for Fallout 4 when you have turned them off:
  
  1. Find Fallout4.exe in the Steam folder to the game. Open Properties->Compatibility, uncheck "Disable full-screen optimisations".
     
  2. Open the Windows Settings System->Display->Graphics, find Fallout 4 in the list of apps, click Options and uncheck "Don't use optimisations for windowed games".
  
  
• The game produces too low or too high frame rates in combination with some displays and their refresh rates. Install the "High FPS Physics Fix" mod:
  
  - F4SE with Address Library (updated!)
  https://www.nexusmods.com/fallout4/mods/42147
  https://www.nexusmods.com/fallout4/mods/47327
  
  - High FPS Physics Fix (updated!)
  https://www.nexusmods.com/fallout4/mods/44798
  
  The High FPS Physics Fix lets your game run at higher frame rates, fixes issues with the game, and includes a load accelerator. If you are unsure about using mods but want to try it then find a good modding guide and read it or watch it.
  
  
• If you do not want to use mods then you can do the following:
  
  
  1. Set iPresentInterval=0 in the game's Fallout4Prefs.ini file to disable VSync.
     
  2. Open the settings to your graphics driver, i.e. Nvidia Control Panel or AMD Adrenalin.
     
  3. Find and open the 3D settings.
     
  4. Open the tab for the individual applications.
     
  5. Find Fallout 4 in the list of applications and games.
     
  6. Enable low latency mode for the game.
     
  7. Set a frame rate limit for the game with a maximum of 60fps.
     
  8. Force vsync to "fast" for the game when you have an Nvidia GPU, for AMD it is called "Enhanced Sync".
  
  This will give you 60fps, thereby keeping the game's physics in check, while giving you tear-free rendering with a high refresh rate display.

• Settings have no effect. Check all 3 .ini files Fallout4.ini, Fallou4Custom.ini, and Fallout4Prefs.ini, for the value you are trying to change. See Additional Notes above for using tools to make changes to the .ini files. These help in avoiding mistakes.
  
• The game cannot find its .ini files. Anti-virus software, Windows' Controlled Folder Access, and OneDrive can interfere with the game. See Additional Notes above.

• The game causes hardware to overheat or to fail. This is not directly caused by a game. Games use DirectX, which uses hardware drivers to access devices. Update drivers and BIOS, especially new hardware needs regular updates. Check for over-heating and avoid over-clocking. Keep a good airflow inside and around your PC. Avoid dust from collecting inside the hardware.

• Meet the minimum hardware requirements, and update Windows and drivers.
  
  
• Clear the folders of Fallout 4, i.e. C:\Program Files (x86)\Steam\steamapps\common\Fallout 4\, clear the AppData\Local\Fallout4\ folder, and remove any .ini files from Documents\My Games\Fallout4\ before doing a reinstall. Be sure there is nothing left over from previous installations, no mods, no old load orders, and no old settings.
  
  
• Verify game files using the Steam client after a new installation.
  
  
• Run on the dedicated GPU, not the integrated GPU.
  
  
• Set the refresh rate to 60Hz, 120Hz or 180Hz. Limit the frame rate to 60fps.
  
  
• Disable High DPI Scaling in Windows and set it back to 100%, or, use the Compatibility tab to the file properties of Fallout4.exe and Fallout4Launcher.exe, and set an override for High DPI Scaling by using the "Application"-setting.
  
  
• Disable video recording and streaming overlays, exit any unnecessary background programs, and check the system tray for unnecessary tools and apps. Turn off animated wallpapers, unplug any unnecessary devices, and so forth.
  
  
• Disable weapon debris when you have an Nvidia card.

Please leave feedback, do not just write "it does not work", but give some details such as your specs, where in the game you encountered the problem, whether it is reproducible or random, how frequent it is, what did you do to cause it, what you have tried to solve it, etc.. Better still, create a thread on the forum and ask specifically for help to your problem. Thank you.