Preheat oven to 375°F; grease a 9x13-inch dish.
Cook macaroni according to package until al dente, adding cauliflower during last 3 minutes; drain and set aside.
Melt 3 tablespoons butter in a large pot over medium; whisk in flour and cook 1 minute, stirring constantly.
Gradually whisk in milk; cook about 5 minutes, stirring frequently, until sauce thickens.
Off heat, stir in 2 cups cheddar, all Gruyere, mustard, salt, and pepper until smooth and melted.
Gently stir macaroni and cauliflower into sauce; pour into dish.
Mix panko with 2 tablespoons melted butter and remaining 1 cup cheddar in a small bowl; sprinkle over casserole.
Bake 25-30 minutes until golden brown and bubbly; rest 5 minutes before serving.