When Mona Lisa Cicciarelli is left at the altar by Joey and his overbearing mother, Alice, Mona Lisa wonders what will be worse - the pitying stares from her friends and family or her parents' renewed obsession with the age of her ovaries and impending spinsterhood. Her father, Chick, tries to fix her up the day after she is jilted with the handsome, Italian-Catholic Dante Coletti, and it's then that Mona Lisa realizes her sanity is at risk. She needs to make a big change, and when she's offered a job opportunity in Atlanta, she consults Noni, her eccentric grandmother - and closest confidante - who gives her the push she needs.
Despite Chick's protests that she is abandoning the family, Mona Lisa escapes to the South, where she moves in with overly compassionate Southern belle roommate Brightleigh and sarcastic New York transplant Amy. She enjoys the South, but her social life is a series of disasters, and Mona Lisa wonders if she will ever live happily married after.