Heat the oven to 375°F and grease a 9-by-13-inch baking dish. Boil the macaroni in water seasoned with 1 tablespoon kosher salt until just shy of al dente, usually 1 to 2 minutes less than the package directions, then drain well without rinsing.

Melt the butter in a large saucepan over medium heat. Whisk in the flour and cook for about 1 minute, then gradually whisk in the whole milk and heavy cream.

Cook the milk mixture for 3 to 5 minutes, whisking often, until it lightly thickens. Reduce the heat to low, add the cream cheese, and stir until smooth.

Remove the saucepan from the heat and add the cheddar, mozzarella, and Gruyère or Monterey Jack a handful at a time. Stir until melted, then season with kosher salt, black pepper, garlic powder, onion powder, and mustard if using.

Fold the drained macaroni into the cheese sauce until every piece is coated. Transfer the mixture to the prepared baking dish and spread it into an even layer.

Combine the panko breadcrumbs with the melted butter and Parmesan, if using. Sprinkle the remaining cheddar over the macaroni, followed by the crumb mixture.

Bake uncovered for 20 to 25 minutes, until the casserole bubbles around the edges and the top is golden. Let it rest for 5 to 10 minutes before serving so the sauce thickens and the pasta holds together.