The movie opens with Maura Ellis (Amy Poehler), a divorced nurse, who mistakenly believes she's about to help a homeless man on the street. Her eagerness quickly turns to embarrassment as she watches him and his friends hop into a truck to return to work. After this awkward encounter, Maura connects with her parents, Bucky and Deanna (played by James Brolin and Dianne Wiest), over Skype. They're preparing to sell their family home, which leaves Maura disheartened. They request that she break the news to her sister, who is likely to react poorly.
Maura’s sister, Kate (Tina Fey), is working from home as a stylist. During a hectic session with a client named Phil (portrayed by Chris Parnell), Kate accidentally ends up ruining his eyebrows just before his date. Her daughter Haley (played by Madison Davenport) arrives, but the visit is short-lived as Kate confesses she was fired for an explosive argument with her boss, causing Haley to leave in haste.
Later on, Kate visits Maura in Florida, and they hatch a plan for Kate to move back in with Maura while they both try to regain their footing. Stopping by a liquor store, they unexpectedly run into Dave (played by John Leguizamo), a despised former classmate who awkwardly attempts to flirt with them.
Upon returning home, they find a "sold" sign on their family house. This revelation sends Kate into a tantrum, showcasing her frustration, while Maura is stunned at the news that their parents have already finalized the sale. Almost all of their childhood belongings have been cleared out, except for their shared bedroom. While sorting through old mementos, they stumble upon their diaries. Kate expresses regret that Maura never had her “big night” in their bedroom, inspiring them to throw one final bash before the house changes owners.
With renewed energy, they embark on a mission to host an unforgettable party, meticulously choosing guests from their old graduating class and excluding Brinda (Maya Rudolph) and Alex (played by Bobby Moynihan), a classmate who often tries a little too hard to be amusing. While shopping for party supplies, they encounter Brinda at a grocery store, who is clearly upset about the lack of an invitation.
The sisters also confront the new homeowners, the Geernts (played by Santino Fontana and Britt Lower), playfully mocking their plans for the house. After treating themselves to mani-pedis, Maura's inviting nature leads her to invite Hae-Woo (Greta Lee) and her friends to the party.
In a serendipitous moment, Maura encourages Kate to seek employment at a local salon, though she is turned away due to her unprofessional nails. While scheming to cancel dinner with their parents, they accidentally interrupt an intimate moment between Bucky and Deanna. Next, Maura has an awkward run-in with a handsome man named James (Ike Barinholtz), and after inviting him to the party, tension begins to build between the sisters as they plan for the night.
As darkness falls, their classmates arrive, including the overly enthusiastic Alex, whose jokes and antics fail to ignite the party. However, the mood quickly shifts when a lively group of lesbians shows up, introducing their own DJ and turning the event into a fun celebration. Brinda, however, is resolved to crash the festivities, leading to confrontations between her and Kate.
In a series of chaotic events fueled by poor judgment and concealed substances—like the arrival of Dave's drug dealer Pazuzu (played by John Cena)—the night spirals out of control. Unbeknownst to them, the party creates unforeseen hazards, including a precious family tree being destroyed and a pool succumbing to a sinkhole incident.
As the night progresses, tensions rise, especially when Kate receives hurtful feedback from Haley, pushing her to resort to drinking. The sisters’ mounting frustrations culminate in a physical altercation that highlights their grievances. In the end, they face the consequences of their reckless actions alongside Bucky and Deanna, who demand they restore the house.
Through teamwork and support from friends, Maura and Kate navigate their battles, ultimately reconciling with each other. As their connection deepens, Maura finds courage to pursue a relationship with James, leading to a sweet moment in which he kisses her.
Fast forward to Christmas, four months later, the sisters arrive at their parents' home for a festive celebration. They embrace each other warmly, symbolizing growth and newfound joy, before breaking into a silly dance that brings levity to their renewed bond.
