Bring a large pot of salted water to a boil. Add 1 pound of large elbow pasta and cook according to package directions until al dente, usually 7-8 minutes. Drain and set aside. Toss the hot pasta with a little butter to keep it from sticking if desired.
In a large skillet, melt 2 tablespoons of butter over medium-high heat. Add the peeled and deveined shrimp, sprinkle 1/2 teaspoon Cajun or Creole seasoning, and sauté for 2-3 minutes per side, until pink and cooked through. Remove shrimp from the skillet and set aside.
In a medium saucepan, melt 3 tablespoons butter over medium heat. Whisk in 3 tablespoons all-purpose flour and cook for about 1-2 minutes to form a roux, stirring constantly to avoid browning. Gradually whisk in 1 1/2 cups whole milk and 1 1/2 cups evaporated milk until smooth and thickened, about 5-7 minutes.
Remove the sauce from heat and stir in 1 teaspoon Cajun or Creole seasoning, 1/2 teaspoon garlic powder, and 1/4 to 1/2 teaspoon black pepper. Gradually add 3 cups shredded sharp cheddar cheese and 3 cups shredded Colby Jack or Monterey Jack cheese, stirring until melted and smooth.
Add the cooked pasta, sautéed shrimp, and 1 cup lump crab meat to the cheese sauce. Gently fold everything together until evenly combined.
In a small bowl, mix 1/3 cup Panko crumbs, 1/3 cup shredded Parmesan cheese, and 1 tablespoon melted butter until well combined.
Transfer the mac and cheese mixture to a greased 9x13-inch baking dish. Evenly sprinkle the Panko-Parmesan topping over the surface. Bake in a preheated oven at 350°F (175°C) for 25-30 minutes, or until the topping is golden brown and crispy.
Let the mac and cheese rest for 5 minutes before serving. This allows the sauce to thicken slightly and makes it easier to portion. Enjoy the creamy, spicy Cajun Shrimp and Crab Mac and Cheese with your favorite side salad or garlic bread.