So actually I think the issue was having an xbox controller plugged in at the same time. I wasn't using it, but every once in awhile I guess it would "take over" and my mouse would lose control. Unplugged it and I haven't had the issue since.
Anyone ever have 1 axis of the mouse just stop working randomly? I've had it happen to both the x and the y. Extremely frustrating when it happens deep into a run. Might be better to ask in the SuperModel3 forums, but I figured I'd check here too.
Update: This happens in regular DOS-Box as well. Sometimes I even get trophies not appearing :( Restarting DOSBox fixes the issue though.
I'm playing in DOSBOX-X. Every once in awhile on Level 5 the jetpack just straight up doesn't appear. Has anyone else ever encountered this bug? Would using a different emulator/version help with this?