Preheat oven to 375°F. Lightly grease a 9x13-inch baking dish.
Bring a large pot of salted water to a boil. Add asparagus and blanch for 2–3 minutes until bright green. Drain and set aside.
In a large skillet, melt ¼ cup butter over medium heat. Add mushrooms and cook until softened, about 5 minutes. Stir in garlic and cook 1 minute more.
Sprinkle flour over mushrooms and stir to coat. Slowly whisk in milk until smooth. Add salt, onion powder, and pepper. Cook 4–5 minutes until thickened.
Remove from heat and stir in mozzarella cheese until melted. Add asparagus and toss to coat. Transfer mixture to prepared baking dish.
In a small bowl, combine panko, Parmesan, and 3 tablespoons melted butter. Sprinkle evenly over casserole.
Bake uncovered for 20–25 minutes, or until bubbly and the topping is golden brown. Let cool slightly before serving.