DeSantis attended the College of Charleston in South Carolina, where she received a Bachelor of Science in Economics and was a member of the International Economics Honors Society. There, she competed on the equestrian team and placed runner-up at the Division I NCAA National Championships. Additionally, she is a three-time national champion equestrian outside of school. Following her graduation from college, First Lady DeSantis worked for the PGA Tour as a producer and on-air host. Additionally, she worked for two Florida television stations in Jacksonville, where she held positions ranging from general assignment reporter, police beat reporter, weekend anchor, and morning anchor. For her work in television, First Lady DeSantis received an Emmy Award for on-air talent and two Emmy nominations: one for an investigative series called Real Life CSI and one for a documentary called Champion, The JT Townsend Story.