Kate (Alexandra Daddario) and Meg (Kate Upton) have been friends since childhood and currently share a cramped apartment in Seattle, where they are both facing personal challenges. Kate, an English teacher, finds herself uninspired and pressured to leave her job by Principal Moss (Rob Corddry), who believes she would thrive in a different career. Meanwhile, Meg, working as a cosmetics salesperson, is struggling to sell dubious North Korean beauty products. One fateful night, the duo decides to drink away their stress, prompting the free-spirited Meg to suggest a vacation to reinvigorate their lives. Although the cautious Kate is initially hesitant, she soon agrees after discovering that Meg has booked non-refundable tickets to Fort Lauderdale using Kate's frequent flyer miles.
Their flight to Florida, however, gets off to a rocky start, with Kate stuck in a window seat while Ryan (Matt Barr), a dashing firefighter heading to a wedding, occupies the middle seat. Both women are immediately smitten and engage in some lighthearted flirting, but Kate's anxiety gets the best of her, causing her to take too many pills and pass out. Shortly into the journey, the plane is diverted to St. Louis due to a hurricane warning, forcing the girls to check into the Sheraton hotel. There, they fortuitously run into Ryan, who invites them for drinks at the hotel club. When the hurricane delays his travel further, the girls take it upon themselves to cheer him up, even engaging in a playful dance-off.
As the next day unfolds, chaos ensues during a hot air balloon ride, where Kate grapples with her fear of heights and Meg inadvertently injures their one-eyed pilot. Things take a turn for the worse when Meg also harms herself after a daring pool trick. Once the hurricane passes, the girls hitched a ride with Craig (Matt Jones), a jewelry salesman who is smitten with Meg but constantly rebuffed. In a series of comedic misadventures, Kate's embarrassing childhood photos become the source of amusement, only for Meg to lock Kate in a gas station bathroom, leading to a rather humorous escape.
As the narrative progresses, the girls take turns in wooing Ryan, leading to a series of misunderstandings, including a car crash orchestrated by Craig after he unknowingly consumes wine laden with sleeping pills. This incident lands the group in a motel for the night, where tensions mount between Kate and Meg, culminating in a dramatic confrontation spurred by jealousy and miscommunication regarding Ryan.
When they learn that Ryan is actually the groom-to-be at a wedding they rushed to stop, the plot thickens. Realizing the wedding is too late to prevent, they confront Ryan, who reveals his complicated relationship history with his fiancée, Genevieve. Rather than expose him, the girls choose to let him be, feeling that his marriage will hold its own challenges.
In the aftermath of their wacky escapades, Meg seeks to mend her relationship with Craig, while Kate decides to redefine her teaching approach, requesting more creative freedom from Principal Moss. Ultimately, both women recognize the importance of independence and personal growth, moving a few blocks away from each other but remaining steadfast friends.
