Sorry to hear about this kind of problem and frustration. Confounding stuff like this is a frequent thing with Blender and 3D.
If you think there’s something wrong with your .blend file, you could try opening a new blank scene and appending the objects from the bad scene file. And if it still doesn’t work, maybe export your simulate-able objects from the bad scene and import them into a new scene. I sometimes use import and export to ‘refresh’ a bad mesh.