St. Luke's College is located in the heart of Sioux City, Iowa, a metropolitan area of approximately 140,000 people. This area is often referred to as Siouxland because it is located where Iowa, Nebraska, and South Dakota meet. The three-state region on the Missouri River has a variety of restaurants, sporting events, entertainment and shopping opportunities. All are within a short drive from the College campus.

St. Luke's College is located on the campus of UnityPoint Health - St. Luke's Hospital. Offering health system-based education in a dynamic setting, the campus houses classrooms, practice labs, a Student Success Center and bookstore, a new Simulation Center, as well as faculty and administrative offices.  Ample parking is also available near the College building.