Preheat your oven to 375°F and lightly grease a 9x13-inch baking dish with cooking spray.
Cook the rotini pasta according to package directions until al dente, then drain thoroughly and return to the pot.
While the pasta cooks, brown the Italian sausage in a large skillet over medium-high heat, breaking it into crumbles with a spatula, until fully cooked and no pink remains, about 8-10 minutes.
Add the cooked sausage, marinara sauce, half of the mozzarella cheese, pepperoni, mushrooms, oregano, and garlic powder to the pot with the drained pasta and stir until everything is evenly combined.
Transfer the mixture to the prepared baking dish and spread it into an even layer, then top with the remaining mozzarella cheese and the grated Parmesan.
Bake uncovered for 20-25 minutes, or until the cheese is completely melted and the edges are bubbling.
Let the casserole rest for 5 minutes before serving to allow it to set for easier portioning.
