After finishing her residency, Dr. Cruz-Knight was a community physician and faculty member for Rush University School of Medicine, then as an attending physician at NorthWest Prime Care Medical Group and later Hegewisch Health Center, Saint Margaret Mercy Hospitals in Chicago. In 2008, she moved to Cleveland and joined University Hospitals Case Medical Center Family Medicine and Community Health at Case Western Reserve University where she was held positions of obstetrics provider, Family Medicine Interest Group Advisor and Director of Pre-Doctoral Programs for the Department of Family Medicine. In 2016, Dr. Cruz-Knight joined the USF-MPM Family Medicine Residency program as the Program Director.