Four best friends, the "Flossy Posse", have grown distant over the years. When lifestyle guru Ryan Pierce (Regina Hall), who is dubbed "the next Oprah", is offered an opportunity to be the keynote speaker at the Essence Music Festival in New Orleans, she decides to bring along her friends to turn her work vacation into a girls' trip. Joining Ryan is Sasha (Queen Latifah), an ex-journalist from Time magazine who now owns a floundering gossip site and is struggling financially; Lisa (Jada Pinkett Smith), a nurse and uptight mom who has not had a boyfriend since her divorce years earlier; and Dina (Tiffany Haddish), a happy-go-lucky, impulsive party animal who was fired after assaulting a coworker shortly before the trip. While on the trip, Sasha is sent a tip that shows a picture of a black man's head kissing an Instagram model, presumed to be Ryan's husband Stewart. The friends are reluctant to tell Ryan, but when Dina spills the news, Ryan shocks them by telling them she is already aware of the situation and that they are in couple's counseling. Nevertheless, when Dina sees Stewart at their hotel, she threatens him with a broken bottle, resulting in her getting ejected and banned from the hotel. In solidarity all the girls leave with her, but the only hotel they are able to get is a sleazy one-star motel frequented by customers of prostitutes..
