If we're going for campy, we might as well go all the way. Despite their status among the most popular enemies in video game history (right up there with Nazis and aliens), zombies have yet to threaten the Mushroom Kingdom. Mario vs. The Unholy Undead could cast plumber and pals as a pack of beleaguered survivors with constantly diminishing supplies, or grant them ever-increasing firepower against wave after wave of shambling corpse. Either way, zombies would be a nice change from the always present koopas, wigglers, bob-ombs, and creepily humanoid shy guys.
We know he'd be able to handle it. The dude can shoot fireballs. He could even use his pharmaceutical know-how to come up with a cure for the outbreak—though he'll never be the same after he's forced to shoot zombie Yoshi in a tearjerking scene toward the game's finale. Allowing a dinosaur that already eats everything in sight to acquire an insatiable taste for human brains is a risk even Mario won't take.