Preheat oven to 375°F and grease a 9x13-inch baking dish.
Cook macaroni according to package directions until al dente. In the last 3 minutes of cooking, add cauliflower florets to the pot. Drain and set aside.
In a large pot, melt 3 tablespoons butter over medium heat. Whisk in flour and cook for 1 minute, stirring constantly.
Gradually whisk in milk and continue cooking, stirring frequently, until sauce thickens (about 5 minutes).
Remove from heat and stir in 2 cups cheddar cheese, all of the Gruyere, mustard, salt, and pepper until smooth and melted.
Add the macaroni and cauliflower to the cheese sauce and stir gently to combine. Pour into prepared baking dish.
In a small bowl, mix panko breadcrumbs with 2 tablespoons melted butter and remaining 1 cup cheddar cheese. Sprinkle over the top of the casserole.
Bake for 25-30 minutes until golden brown and bubbly. Let rest 5 minutes before serving.