Greg Focker (BEN STILLER) is a Chicago-based male nurse who's about to propose to his schoolteacher girlfriend, Pam Byrnes (TERI POLO), when she gets a call from her sister, Debbie (NICOLE DEHUFF), stating that she just got engaged. Upon hearing that her fiancé, Dr. Bob Banks (TOM McCARTHY), first asked permission from their overprotective father before popping the question, Greg realizes he has to play his cards just right when he finally meets Pam's parents.
He gets that chance when the two of them then fly to the east coast two weeks later for Debbie's pending wedding. Understandably nervous and arriving with only the clothes on his back since the airport lost his luggage, Greg manages to impress Pam's mother, Dina (BLYTHE DANNER), but isn't quite as successful in doing the same with her father, Jack (ROBERT DE NIRO), a man supposedly in the rare flowers field.
Due to Jack's imposing demeanor and fielding of questions that near that of an investigative probing, Greg begins to feel more at unease, particularly after Jack shows him the miniature hidden surveillance cameras he's developed. Upon meeting Pam's brother, Denny (JON ABRAHAMS), and Debbie's future in-laws, Larry (JAMES REBHORN) and Linda Banks (PHYLLIS GEORGE), not to mention Pam's wealthy and resourceful ex-fiancée, Kevin Rawley (OWEN WILSON), and facing a series of mishaps that grow progressively worse with each occurrence, Greg soon finds that getting along with his potential, future in-laws might not be as easy as it once seemed.