Bring a large pot of salted water to a boil, add the macaroni, and cook 1–2 minutes less than package directions until just slightly firm. Reserve 1 cup of pasta water, then drain and set aside.
In a heavy-bottomed saucepan, melt butter over medium heat, then whisk in flour and cook for 2–3 minutes until the mixture is smooth, lightly golden, and smells faintly nutty.
Pour the warmed milk into the roux in a slow, steady stream while whisking constantly, then add the heavy cream and bring to a gentle simmer over medium-high heat, whisking frequently for 5–7 minutes until thickened to a gravy-like consistency.
Reduce heat to low, add the cream cheese and whisk until smooth, then add the cheddar one handful at a time, whisking after each addition, followed by the Parmesan, Dijon mustard, garlic powder, onion powder, salt, pepper, and nutmeg.
Fold the drained pasta into the cheese sauce until every piece is fully coated, adjusting consistency with reserved pasta water if needed, then let rest 2–3 minutes off the heat before serving.
Preheat oven to 350°F (175°C), pour the mac and cheese into a greased 9x13-inch baking dish, top with shredded cheddar and optional buttered panko, and bake uncovered for 20–25 minutes until golden and bubbling. Rest 5 minutes before serving.