Hard-to-crack ex-CIA man Jack Byrnes and his wife Dina head for the warmer climes of Florida to meet the parents of their son-in-law-to-be, Greg Focker. Unlike their happily matched offspring, the future in-laws find themselves in a situation of opposites that definitely do not attract.

Filmmaker Nicky offers to track down the son that Mamie gave up for adoption nearly two decades before. Meanwhile, Mamie's stepbrother (and the father of her child), Charley, along with his boyfriend, Gil, try to find out what became of the sperm Gil donated to a lesbian couple. Finally, singer Jude becomes entangled in a love triangle with androgynous drummer Otis and his conservative father.

When a down-on-his luck father of three has Hollywood buzzing over his screenplay, it's a matter of time before all his dreams come true. However, his dreams are short lived when a pair of shady film makers con him out of the rights and he has no choice but to join forces with an unlikely partner, a drug lord who has plans of his own for this upcoming screenwriter.