Cook penne in a large pot of salted boiling water according to package directions until al dente. Drain and reserve 1/4 cup of pasta water.

Toss beef cubes with Cajun seasoning in a bowl until evenly coated.

Heat olive oil in a large skillet over medium-high heat. Sear beef bites for 4 to 5 minutes until browned on all sides. Remove beef from skillet and set aside.

In a saucepan over low heat, combine cubed Velveeta and milk. Whisk constantly until the cheese is melted and the sauce is smooth.

Whisk garlic powder and onion powder into the cheese sauce.

Add the cooked penne to the cheese sauce, adding a splash of reserved pasta water if needed to adjust consistency. Toss until fully coated.

Portion the cheesy pasta into bowls and top with the seared Cajun beef bites.