In the aftermath of Thanksgiving, Eliza, portrayed by Hope Davis, stumbles upon a mysterious love letter containing a poem that insinuates her husband Louis, played by Stanley Tucci, is involved in an affair with a woman named Sandy. Fueled by suspicion and determination, she resolves to travel to New York City to confront him, and her entire family joins her on this unexpected journey. The family packs into their station wagon for a ride from Long Island, including her parents, Jim and Rita — the former played by Pat McNamara and the latter by Anne Meara — her sister Jo, portrayed by Parker Posey, and Jo's live-in boyfriend Carl, played by Liev Schreiber. As they embark on this tumultuous drive, Carl shares snippets about his latest writing project, an eccentric surrealist narrative involving a man with the head of a dog who gains notoriety from his extraordinary deformity and uses that fame to espouse his political beliefs.
Once they arrive in the city, Eliza and Rita make their first stop at Louis's publishing firm. As they wait for news about his whereabouts, Eliza encounters Eddie Masler, portrayed by Campbell Scott, a writer who enlightens her that the poem in question is titled "The Definition of Love." Just when Eliza is about to lose hope, Louis's boss informs her that he might be attending a book release party later that evening. In an act of desperation, Rita decides to investigate Louis's office, where she discovers a photo from a birthday celebration featuring Louis alongside a woman, heightening Eliza's suspicions.
Their quest leads them to Louis's apartment, where they witness him exiting with the same woman from the photo, presumed to be Sandy. In a frantic attempt to follow them, they become stalled at a traffic light, losing sight of them altogether. Unfazed, Rita rushes out to pursue them but ultimately collapses on the sidewalk from exhaustion. Fortunately, Carl asks for help from a kind stranger leaving the nearby apartment, leading to an unexpected encounter with a father and son duo who come to Rita’s aid. The son, however, inadvertently reveals unsettling details about his father's neglect of his alimony responsibilities, casting a shadow over their brief hospitality.
Not disheartened, the family proceeds to Louis's anticipated book release party. While Carl and Jo head inside to search for Louis, the others remain behind in the vehicle. At the party, they find no sign of Louis, but Jo and Carl bump into Eddie, leading to a flirtatious interaction between Jo and Eddie. Their conversation quickly turns contentious when Carl's controversial opinion surfaces — he believes America should adopt an aristocracy rather than uphold its democratic values, sparking a heated argument with Eddie.
With no success in spotting Louis at the party, the siblings eventually make a hasty exit. However, Jo realizes she left her bag behind and returns to the venue, where she encounters Eddie once more, culminating in a spur-of-the-moment kiss. After Jo departs, Eddie charmingly leaves his phone number in her phone book, suggesting a potential romantic connection.
The family reconvenes and makes their way back to Louis's apartment. Eliza enters to discover that a party is already in full swing at his place. While anxiously waiting, Jo secretly calls Eddie from a payphone, telling Carl that she's merely checking her messages. Observing this, Carl's jealousy ignites an argument, resulting in Jo openly expressing her disdain for him.
As tensions rise, Eliza catches sight of the woman she believed to be Sandy, only to soon realize that she is mistaken. In a shocking turn, she ascends to the roof and witnesses Louis locking lips with the real Sandy — only to her utter disbelief, Sandy is revealed to be a man. Enraged and heartbroken, Eliza storms out of the apartment, leaving her family aghast at the revelation. Rita insists that Eliza get back in the car, but Jim urges her to express her true feelings instead of adhering to Rita’s demands. The scene unfolds with Eliza's confrontation with Louis, their argument escalating until Jo, showing her solidarity, rushes after her sister as the rest of the family remains parked, bewildered. The profound moment encapsulates a sense of unity, as the film concludes with the sisters walking away together into the vibrant backdrop of the city, symbolizing resilience in the face of betrayal.
