-Really long save/load/preview times since all layouts, backgrounds, tilesets, etc. are internal.
-Won't be able to have team members build levels unless you buy a C2 license for each one and use SVN or something.
-Each layout has its own layers & properties so unless you duplicate levels & erase everything to start fresh or make a template of sorts you might spend a lot of time setting these up.
-Will have to rebuild all your levels if you decide to switch to another game maker.
-You'll probably have to - in every layout - place a trigger at each door telling it which layout to go to next and which door to create your player at. You'll also have to save your player's variables between rooms if you want the transitions to be convincing. It's difficult but that can be completely avoided using your own editor by loading a whole area at once but creating/destroying rooms individually.
-Can't use tiles.
It's just bad news. Back when I used MMF I tried making a 'vania using a frame for each individual room and it was a mess. It's certainly more feasible in CC/C2 but I wouldn't recommend it unless the game was really small.. Like A Mini Falafel Adventure or something.