At popular South Beach University (Miami), filthy rich super-snob Victoria English is the absolute queen of leading Greek student club, Sigma Sigma. In order to achieve her crowning ambition, winning FHM Magazine's annual best sorority, she must recruit atypical 'Sigmies' to fulfill the diversity criteria. Ambitious sycophant pledge Kristen Haas helps her attract 'losers' (too poor, ugly, unfashionable), who are cruelly put through excruciating hazing, without intent to actually enroll them. Gloria, the brightest and most assertive pledge, wins the heart of Derek 'baby Dick', Victoria's ideal, yet constantly abused boyfriend, whose bitch-addiction is cured by this alternative lover. Together they lead the revolt of the not-even-nerds.

Nacho (Black) is a monastery cook, who spends his day feeding orphans and being overlooked by the monastery. When Sister Encarnación (Reguera) arrive at the monastery, Nacho realises that the only way to win her affection and to save the children, will be by competing as a Luchador wrestler.

The movie will shift its focus on Erik Stifler, the cousin of Matt and Steve, a youngster who is nothing like his wild relations. Peer pressure starts to turn him to live up to the legacy of the other Stiflers when he attends the Naked Mile, a naked run across the college campus. Things get worse when he finds that his cousin Dwight is the life of the party down at the campus.

In Chicago, the art dealer Brooke Meyers feels not appreciated and neglected by her immature boyfriend Gary Grobowski, who is partner of his two brothers in a tourism business, and decides to break-up with him to make Gary misses her. Gary misunderstands her true intention, both follows the wrong advices of family members and friends, beginning a war of sexes with no winner.

In Ohio, Priscilla Chase is the VP of a company that works bringing new business to Cleveland. She has been married for more than ten years with Jack Chase, the biology teacher from the local public school. Priscilla is successful in her career but is frigid and has never reached an orgasm, hurting her frustrated husband. When Priscilla decides to buy a vibrator, Jack is seduced by his teenage student Kristen Taylor and recovers his self-esteem, working out, losing weight and dressing adequately. Priscilla has new sexual experiences and becomes closer to Wayne the Pool Guy, the constructor of swimming pools in her neighborhood since she was a child. The new relationships upgrade the personal and professional lives of Priscilla and Jack.