If you're talking film the answer is film has literal grain because it's physical.
If you're talking digital the answer is sensors use gain to increase and decrease sensitivity. When you increase the gain you start having cross-talk as you overload individual pixels and the detection kinda bleed across them.
That's a very broad simplified explanation as I understand it.
So I saw you were using Pixel Shift and that's why you can't use strobes.
Another solution is just change your technique and do the post-processing manually. There are plenty of tutorials online that show how to do super-resolution by simply taking a lot of images and stacking them in Photoshop.
If you do it right you can take a 10 MP camera shooting at 200 ISO and make a 100 MP image at relative 10 ISO. You just need to take a bunch of photos and stack them.