It's been two years since Tom (STEVE MARTIN) and Kate Baker (BONNIE HUNT) moved their family to Chicago and their kids are getting older, much to the dismay of Tom. Oldest daughter Nora (PIPER PERABO) is pregnant and she and husband Bud (JONATHAN BENNETT) are about to move to Houston. Oldest son Charlie (TOM WELLING) is working as a mechanic, while Lorraine (HILARY DUFF) has just graduated and is headed off to New York for an internship at a fashion magazine. Sarah (ALYSON STONER) is still a tomboy, but her newfound interest in boys means those days are numbered.
Meanwhile, the rest of the kids -- Mark (FORREST LANDIS), Jake (JACOB SMITH), Henry (KEVIN G. SCHMIDT), Kim (MORGAN YORK), Jessica (LILIANA MUMY), Mike (BLAKE WOODRUFF) and twins Nigel and Kyle (BRENT & SHANE KINSMAN) -- are all getting older and don't need their parents quite as much as they once did.
Accordingly, Tom thinks it would be a good idea for them to head for Lake Winnetka, Wisconsin -- one last time as a complete family -- for some end of the summer vacation. When they arrive, they find that their favorite rustic cabin is more rundown than they remember, especially when compared to the elaborate lake-front mansion owned by Jimmy Murtaugh (EUGENE LEVY). He and Tom grew up together, and their competitive ways resume right where they left off.
Jimmy is married to wife number three -- the much younger Sarina (CARMEN ELECTRA) -- and also has a large number of kids. They include teenager Anne (JAMIE KING), who thinks her dad's highly disciplined ways are stifling her, and eighth-grader Eliot (TAYLOR LAUTNER) who takes a liking to Sarah. With Jimmy trying to impress, better and defeat Tom any way he can, that only brings Tom down to his level, all leading to a big family competition between them.