Can't play modded Fallout 4 due to crash to desktop

Happend to me as well - solution which worked for me is below.

Targets:

• Avoid reinstall of the game
• Keep all players settings in save untouched

1) Situation description

• Game was modded (> 80 mods), but with fully functional saving system
  • Suddenly without any change in the game or Nexus, the game was crashing to desktop without any information during saving
  • save files were suddenly saved as *.fos.tmp instead of *.f4se and .fos (save files in C:Users*userDocumentsMy GamesFallout4Saves)

2) solution, which worked for me (chronologically)

• Created backup of saves
• Switched off all "Plugins" in Nexus (Plugins, not the mods!)
• Splitted "plugins" into 2 halfs and first half switched back on
• Try to save the game and because of OK save process, I splitted the remaining part into 2 halfs and switch of one half only (it means 1/2 + 1/4 of plugins were switched on)
• I was using quicksave for functionality check (quicksave of "original" save)
• With this method was gradually switched on plugins and at the end was identified mod, which suddendly was causing the problem with saving
• At the end I tried to switched on the "problematic" and save was suddenly functional as well, despite that before it was clearly causing the problem

Nevertheless the game is saving again. I hope, that it was helpful for someone.

I had to get rid of all four Rising City mods, Unique NPCs / Monsters, and (I don't see it there but, sparingly use Awesome Follower Tweaks to make new followers). Most of those would cause memory related CTDs all by themselves, but after uninstalling them I no longer have save bloat problems.

If a save game CTDs on loading it, check if the save file is about >60 megs. Mine hover around 30~40. If you see a spike in size comparative to the list of saves then it's bloated (and sadly already has been borked for some time now).

Delete the bloated save files. When you finally do get an older save to load, immediately try to save the game. If that save is borked too, it will crash. You can keep deleting saves until you find one that will save, but in all likelihood (you'll lose about ten hours) as you approach the same amount of in-game time or trouble locations, it will crash or save-bloat again.

Uninstall at least those four mods and make a new game.

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And if you want to play F4 heavily modified into reality, start with getting Darker Nights, and Interior Lighting Overhaul. You don't really need new locations to enjoy F4 again, just the same chance of falling off a cliff because you can't see anything, or dying from radiation because you haven't showered (Get Dirty), than you have of getting shot.

You'll also want a 'flashlight' mod that extends the light casting range of headlamps and PA (not the pipboy light). You'll just have to pretend that using it completely gives away your position, which it doesn't.

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I have the maximum amount of plugins that you can have: 255. The 'divide them into two' isn't an option I'd enjoy trying. You don't just throw 255 mods at F4, you install a few at a time and play the game. If the game breaks, it's in one of the sets you just installed.

That's also more for CTD on game start up, not loading a save. And if you find a mod that you have to remove, it's time to start a new game. Additions mid game are ok, removal is not. Undoubtedly it's my load order that CTDs the game 9 out of 10 times every time I try to start the game exe, but once past that, it's smooth sailing until War of the Commonwealth spawns too many npcs.

"Suddenly without any change in the game or Nexus" : CTDs. That was a problem you created when you installed a mod and it's finally rearing its head (or you don't have it blocked in the firewall, or haven't told Steam to shove their updates back where they got them). If you don't have a save with twenty hours on it, having started with all the mods already in question, it's still an unverified-to-be-stable installation, and you shouldn't have moved on to installing the next set of mods.

If you use mod organizer you can sort out the buggy mods with the testprofile method. Make about 6 testprofile copies of your current profile and use them to find the buggy mod(s) by testing with nested intervals. Load your save after each activated interval and check if the bug/ctd still appears in this interval. If not you can sort out this part of your tested mod list and so on.

If you play with NVIDIA turing card, be sure to set the weapon debris option in gamelauncher to "off". These cards will raise ctd if this option is somehow activated. Check also prefs.ini for [NV Flex] tab, all values should be set to "0".