01 - Preheat the oven to 400°F. Line a baking sheet with parchment paper.
02 - Arrange butternut squash cubes on the prepared baking sheet. Drizzle with 1 tablespoon olive oil, then roast for 20 to 25 minutes until squash is tender and lightly browned.
03 - Fill a large pot with water, bring to a boil, and salt generously. Cook the macaroni according to package instructions until al dente. Drain and set aside.
04 - In a large saucepan, melt 2 tablespoons butter over medium heat. Add diced onion and sauté for 3 to 4 minutes until softened. Stir in minced garlic and cook an additional minute.
05 - Add roasted butternut squash to the saucepan with onions and garlic. Pour in whole milk and heavy cream. Simmer for 5 minutes, then puree the mixture using an immersion blender or transfer carefully to a standard blender until smooth.
06 - Stir in shredded cheddar cheese, grated Parmesan, salt, black pepper, nutmeg, and smoked paprika. Mix until the cheese is melted and the sauce is creamy and smooth.
07 - Return cooked pasta to the saucepan. Stir thoroughly until all pasta is evenly coated with the sauce.
08 - Transfer mac and cheese to a greased baking dish. Toss panko breadcrumbs with melted butter and sprinkle over the top. Bake at 400°F for 10 to 12 minutes, or until topping is golden and crisp.
09 - Portion while hot and, if desired, garnish with additional Parmesan or chopped fresh parsley.