Thirty-five-year-old Tripp still lives with his parents Al and Sue in Baltimore. His best friends Demo and Ace also still live in their parents' homes and seem proud of it. Tripp has many casual girlfriends. When he's tired of them, he invites them to “his place"—and when they realize he still lives at home, they promptly dump him.
Al and Sue are fascinated when their friends, whose adult son recently left home, reveal they hired an expert to get him to move out. The expert is Paula, who believes that men continue to live at home because they have low self-esteem. Her approach is to establish a relationship with the man to build his confidence, then transfer his attachment from his parents to her.
However, Tripp does not fit her previous profiles, as he has normal social skills, good self-esteem, and a good job he enjoys. After an awkward encounter with his parents, Paula thwarts Tripp's attempt to dump her and has sex with him, while developing real feelings. She and Tripp find themselves in unfamiliar waters and confide in their friends.
Paula's vocation exasperates her roommate Kit, who thinks Paula became a con artist because a man who lived with his parents broke her heart. But later Paula is shocked to learn why Tripp lives at home: His life collapsed when his fiancée suddenly died, and his family has been his solace ever since.
Ace discovers what is going on and blackmails Paula for a date with Kit. Although Kit is more attracted to Demo, she and Ace wind up falling in love. Ace then "outs" Paula to Demo, who then tells all to Tripp. Tripp angrily confronts his parents over the scam and breaks up with Paula. Wracked with guilt, Paula refunds Al's and Sue's money. After an awkward confrontation, Tripp has moved out and taken up residence in the sailboat he's been saving for. Over time he forgives his parents, but can't forgive Paula.
Tripp's parents and friends devise a plan to reconcile the two. They tie up and gag him, locking him and Paula together in a room. Paula pours her heart out, and he finally forgives her. The film ends with Al and Sue in their empty nest, happily singing "Hit the Road, Tripp". This fades into the closing credits over the Ray Charles song "Hit the Road, Jack", and we see Tripp and Paula sail away on his newly purchased boat.
Matthew McConaughey as Tripp
Sarah Jessica Parker as Paula
Zooey Deschanel as Katherine "Kit"
Justin Bartha as Philip "Ace"
Bradley Cooper as Demo
Terry Bradshaw as Al
Kathy Bates as Sue
Adam Alexi-Malle as Mr. Axelrod
Tyrel Jackson Williams as Jeffrey
Katheryn Winnick as Melissa
Rob Corddry as Gun Salesman
Patton Oswalt as Techie Guy
Mageina Tovah as Barista
Stephen Tobolowsky as Bud
Kate McGregor-Stewart as Bev