After awakening with a hangover, Edina 'Eddie' Monsoon frantically prepares to launch a major fashion show. Meanwhile, her unsympathetic daughter, Saffron—whom Edina had promised to quit drinking—constantly reprehends her mother's unhealthy habits. Edina's best friend, Patricia 'Patsy' Stone, arrives to accompany her to work. At the office, Edina's assistant Bubble reports that one of the main models, Yasmin Le Bon, has dropped out, while Princess Anne has replaced Princess Diana on the guest list. Edina subsequently manages to cajole several B-list celebrities into attendance, turning the show into a rousing success. Later that night, Edina and Patsy indulge in a drunken bender—much to the disgust of Saffron, who locks Edina out of the house. The next morning, Edina and Patsy trick Saffron into believing that Edina is going to check into a rehabilitation clinic.

Unable to fit into the majority of her clothes, Edina becomes determined to lose weight. At the office, she is horrified upon learning of an upcoming visit by Penny Caspar-Morse, a thin model that used to torment Edina about her weight. Edina unsuccessfully attempts to exercise, and with Penny arriving earlier than expected, she accepts Patsy's suggestion to undergo a liposuction. After a disturbing nightmare about the procedure going horrifically wrong, Edina decides against the idea and instead puts on an oversized sweatshirt in order to cover herself up. Patsy announces that Penny is blind, much to Edina's delight. Later, Edina drunkenly rants at Penny about how she ruined her life and brags about how successful and thin she has become. However, she inadvertently reveals her weight as she grabs Penny's hands and places them on her waist.

Edina & Patsy go on holiday in France, where they find themselves staying in a rustic cottage, instead of the château they were expecting. There is no food or wine, and the duo are constantly disturbed by an old Frenchman whose French they cannot understand. They are later rescued by Saffron, who arrives with supplies. Bubble comes along to deliver an urgent message concerning Edina's home decorating business, but she forgets about it. When Saffron reminds Bubble about the message, Edina panics and rushes to return home. The old Frenchman stops by again and repeats his message to Bubble, who understands perfectly that Edina and Patsy have been staying in the wrong place, and were expected in the château down the road. Later, customs detains the group when a suspicious white powder is found in Patsy's luggage, but they are freed when the powder turns out to be a harmless substance. Patsy, instead of being relieved, is horrified as she realises she actually enjoyed playing ping-pong.

Edina is none too pleased about her 40th birthday. As opposed to the glamorous, star-studded surprise party she had hoped for, Edina is disappointed to learn that Saffron has planned a quiet lunch with family and friends—including both of Edina's ex-husbands, Justin and Marshall, and their respective new lovers, Oliver and Bo, as well as Patsy and Mother. Edina behaves erratically during the party, switching between self-pity and spite, and she soon provokes Oliver, her least favourite guest, into making an angry exit. Justin and Marshall are shocked to discover that they have both been paying alimony to Edina. While Edina and Patsy sing drunkenly on a new karaoke machine, Justin and Bo secretly plot to cut off Edina's alimony.

Patsy, who is temporarily staying with the Monsoons, becomes jealous when Edina reconnects with an old boyfriend. During one of her sporadic appearances at work, Patsy is assigned to host a fashion makeover segment on a morning television show. After clashing with the models, Patsy attempts to persuade Saffron and Mother to appear on the show in their place, telling a tale of her emotionally distant mother. Saffron agrees, on the condition that Patsy moves out of the house and does not interfere with Edina's relationship. Patsy's television appearance turns disastrous as she suddenly becomes nervous. After Patsy convinces Edina to break up with her boyfriend, Saffron lashes out at Patsy for not upholding her end of the deal.