Heat oven to 350°F. Lightly grease a 9x13-inch baking dish.
Boil macaroni in well-salted water until just shy of al dente. Drain and set aside.
Stir panko, Parmesan, and olive oil in a small bowl until evenly moistened. Set the topping aside.
Melt butter in a large pot over medium heat. Sprinkle in flour and whisk until smooth, about 1 minute.
Slowly whisk in milk and half-and-half. Simmer, whisking, until the sauce thickens and coats a spoon.
Season the sauce with Dijon, garlic powder, onion powder, paprika, salt, and pepper. Adjust to taste.
Take the pot off heat. Stir in cheddar, Monterey Jack, and cream cheese until smooth and glossy.
Fold the drained macaroni into the cheese sauce until every piece is coated.
Spread the mac and cheese into the prepared dish. Sprinkle evenly with the panko mixture.
Bake until bubbling at the edges and the top is golden, 18–22 minutes. Rest 5 minutes before serving. Garnish with parsley.