塔米（梅丽莎·麦卡西 Melissa McCarthy 饰）岁数不小，生活却越过越惨淡，一场意外让她失去了爱车，之后，在工作中又惨遭上司解雇。接二连三的打击和挫折让她心灰意冷，当她想要在丈夫身上寻求温暖和安慰时，却发现丈夫竟然有了情人，更让塔米崩溃的是，这位情人竟然就住在他们家隔壁。 　　人生走入了死胡同，塔米感到走投无路，正当她陷入绝望之时，她的外婆帕尔（苏珊·萨兰登 Susan Sarandon 饰）来到了塔米的身边。然而，帕尔的到来并没有给塔米带来快乐，因为帕尔是一个酗酒又粗鲁的老太太。帕尔让塔米带她去尼加拉瓜大瀑布旅行，就这样两人踏上了注定不会平静的旅途。Tammy, who was recently fired from a Topper Jack's fast food restaurant, returns home only to find her husband enjoying a romantic meal with the neighbor. She quickly packs her necessities, and travels down three houses to her parent's home. Upon denied use of her mom's car to drive to Niagara Falls, she quickly resorts to an "ailing" grandmother, who also lives in the home...Only instead of traveling alone, Grandma Pearl wants in on the road trip. After realizing Grandma Pearl has the funds, they hit the road. Pearl soon proves to be quite the alcoholic despite her diabetes, and Tammy quickly turns into the "baby-sitter." From finding love in a bar to robbing a Topper Jack's in order to bail Pearl out of jail,the quirky adventure will have you finding yourself riding along for the misadventures of Tammy.