After a car accident, Peter, Brian, Joe, and Quagmire wake up in a hospital with no memory and discover that they're the last people left on Earth.
Peter and Lois' marriage hits a bit of a snag. When Brian wins the New England Rising Writer's award, the three of them head to Martha's Vineyard for a nice relaxing vacation. Peter's usual drinking habits take over and he soon spirals out of control, as does Brian's self restraint, as he soon professes his love for Lois. Peter and Brian test their friendship over the woman of their dreams.
When Peter gets a free gas card, the family decides to hit the road on vacation, but they accidentally leave Stewie behind; home alone, Stewie soon runs out of food and diapers, and is forced to take a job.
After seven years of pregnancy, Bonnie gives birth to baby Susie, and Stewie immediately falls in love; but when Joe can't pay the massive hospital bill, Peter and the boys plan to rob Mr. Pewterschmidt.
Lately Peter hasn't been able to perform very well in the bedroom. So he asks Quagmire and Joe to step in and help him get his mojo back.
Meg is worried that she won't do well on her SATs, so she convinces Brian to take the test for her. A confident Brian agrees to the challenge, and even dresses up like Meg, only to find out that he received the lowest score in the class.
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