I have barely used them, so I’m not the best at explaining, but for me it boils down to a number of things.

First, TWMs are meant to work with keyboard shortcuts more than with any mouse input. Easy for those to conflict with the shortcuts of your app.

Second, compatibility might be an issue if your TWM doesn’t use a normal compositor. I don’t know how well something like Blender would render its UI on a TWM.

Third would be that a lot of creative apps are not meant to be tiled by the system and have their own solutions for window management, which could conflict with the TWM.

I’m sure there are more reasons. I can’t think of them just now.