Gaylord "Greg" Focker and his wife Pam, daughter of a retired CIA agent, now have five-year-old twins. The film deals with how Greg and Pam raise their children.

Greg goes through a midlife crisis as he ponders the rest of his life, especially the issues of being a good father and provider. Greg's father-in-law Jack reactivates his high suspicions about his son-in-law, now the father of his grandchildren. The high-level tension between Jack and Greg goes full-force again, heading to another major showdown.