When the family causes Marge to flip out, she takes a vacation from it all at Rancho Relaxo, leaving Lisa and Bart with Patty and Selma, and Homer alone with Maggie. Then, Maggie goes searching for Marge while Homer struggles with the former-duties of his wife.
Marge has been under a lot of stress at home since the family takes her for granted, and she lashes out by clogging up traffic at the Springfield Memorial Bridge, and causing all of Springfield to see when it is placed on the news (although there is plenty of bumbling as Kent Brockman is bonked around and Arnie Pye drops his bagel). She is placed under arrest by Chief Wiggum, but Mayor Quimby, in a political gambit, pardons her. Later on, Marge sees a TV commercial for a resort spa called "Rancho Relaxo", and decides that she needs a vacation. Homer tries to talk Marge out of it by reminding her of failed family vacations from the children's misbehavior and how they ended up staying home because of it. She convinces him that she needs to go to Rancho Relaxo alone so she can relax. Marge puts Bart and Lisa into the care of Patty and Selma, but Maggie cries and clings to Homer when she is about to be deposited at her aunts, leaving Maggie in Homer's care.
Bart and Lisa are having pain in the care of Patty and Selma. Bart has to sleep with Patty, who snores, as Lisa has to sleep with Selma. Homer finds it troublesome feeding Maggie, and changes Maggie's diaper by closing it with a staple gun. As for entertainment, Homer tries to make Maggie laugh through a puppet show, only to scare Maggie. Santa's Little Helper attacks both the puppets and Homer, to which Maggie applauds and laughs.
Homer later invites Barney over to help him, but realizes how much he needs Marge to take care of things, especially when the following morning Homer finds Maggie has gone missing. Maggie left the Simpson house by herself as she was distressed at the absence of Marge. Homer and Barney then look for Maggie, but can't find her. Homer calls the Department of Missing Babies, goes to Marge's sisters to ask Bart and Lisa if they have seen Maggie. As they haven't, but try to make it clear they're desperate to get away, after being put into slavery having to rub the sister's feet. After a long search from Homer and Barney, Homer calls the police to help him. Marge, having thoroughly enjoyed her vacation, calls it quits, and calls Homer. Telling him she is feeling much better, Homer then asks how she would feel if Santa's Little Helper would have run away. Marge then retorts saying that would be awful, after which Homer tells her the "good news" the dog hadn't run away. Relieved, Marge reveals she's coming back and Homer should pick her up in one hour at the train station.
Maggie is then found on the edge of the top of an ice-cream shop by the police. Chief Wiggum thinks she is trying to commit suicide, but she is actually sleeping next to the statue of an ice-cream cone that looks like Marge's head.
Not knowing the police have found Maggie, Homer prepares to apologize to Marge. He first talks to himself, saying: "Marge, Maggie was very young. It's not like we got so attached to her...", but doesn't agree with it. Chief Wiggum then reveals himself from behind the door and returns Maggie to Homer. Homer then duct-tapes Maggie to her car seat, securing her tightly, and makes his way over to Patty and Selma, to pick up Bart and Lisa. Overjoyed with his presence, they cling onto his feet, having Homer kick them into the backseat.
On the train, Marge glances at a photo of her family, comparing it to the lesser-good looking family that greets her. In the evening, Marge says she appreciates Homer helping her around the house, to which Homer gladly agrees. Marge then continues staying her requests, upon which Bart interrupts her, showing the kids are sleeping in with their parents. The family then calls it quits, and goes to sleep.