Foxy, Xandir, Captain Hero, Clara, Ling-Ling, Wooldoor, and Spanky all return to live in the newly-rebuilt house, along with 4 (later 3) new housemates. The animation style remains how it was in the first three seasons. The intro for season 4 is the same one from season 3, only with Piper, Pucker, and Maya added before the title card, and the Clips are slightly shorter (and Fran in place of Toot for the first 3 episodes). The show keeps it's TV-MA rating (though in syndication, reruns are heavily censored, toning it down to a TV-14 rating). Toot returns in the third episode. Season 4 willl premiere worldwide.
- Princes Clara (voiced by Tara Strong): Age 20. A racist and homophobic spoof of the Disney Princesses. She often gets into fights with Foxxy due to her racist tendencies, though is good friends with her and Xandir.
- Wooldoor Sockbat (voiced by James Arnold Taylor): Age 13. A poorly conceived Spongebob parody. He is shown to be younger than the other housemates
- Foxxy Love (voiced by Cree Summer): Age 23. A promiscuous mystery solving musician. Her Humor revolves mostly on her sexual habits.
- Toot Braunstein (voiced by Tara Stromg): Age 20. An overweight former sex symbol. She is an alcoholic, and is often seen being brutally shot (and on one occasion, murdered) by Piper for stealing her vodka. Toot and Clara become more sympathetic this season as the role of the show's mean spirited character is largely taken over by Piper.
- Xandir (voiced by Jack Plotnik): Age 19. A parody of video game characters, particularly Link from the Legend of Zelda.
- Ling-Ling (voiced by Abbey DeGregorio): An insane homicidal spoof of Pokemon, though he has been shown not to be as insane as Piper, or as homicidal as Pucker. When scanned by Pucker, his sensors labeled Ling-Ling (along with Spanky and Piper) as bisexual, though until season 4, he hadn't displayed any bisexual tendencies,
- Spanky Ham: (voiced by Adam Carolla): Age 31. Much of his humor revolves around his crudeness. He has been indicated on throughout the series that he is bisexual.
- Piper Vanna (voiced by Grey DeLisle): Age 18. A blonde haired psychotic Jewish girl, who wears black clothing with cutouts, and a black thong. Much of her humor revolves around her psychosis, her alcoholism, and her addiction to various drugs. She is a big fan of the show, and went crazy(er) with excitement when she was chosen as a housemate for the 4th season. She has shown amorous affections towards her housemates (male and female). She is also very mean spirited, and sleeps in a bed identical to Foxxy's. She keeps a loaded revolver gun with her at all times, which she often uses to shoot people. Often the other housemates. She also has a life-size Ling-Ling costume that she can strangely fit into. She seems to show the most interest in Spanky, Foxxy, and Maya. She is often shown drinking or smoking a cigarette (seemingly uncaring that smoking could potentially kill her). She seems to be fond of Spin-the-bottle, which she mostly uses as an excuse to hook up with her housemates.
- Fran Peters: (voiced by either Tara Strong or a guest actor): Age 20. a big-haired parody of Lamb Chop. She is often considered similar to Toot Braunstein. She joins the cast in the first episode of season 4, and stays until she is eaten in the third episode by Toot.
- Maya Banerjee An Indian lesbian girl who joins the cast in season 4, though she lacks an Indian accent. She often shows an interest in Foxxy and Piper, and has slept with both. She and Xanidr are the only housemates not implied to be bisexual
- Pucker (voiced by Jess Harnell): A homicidal robotic spoof of PAC-Man. Despite being a robot, he is shown to be able to feel pain and sexual pleasure, and to taste. Like most ofthe other housemates, he has been implied to be bisexual, as he was seen having sex with Xandir (with Pucker on the receiving end of the affair), during which he can be heard moaning in pleasure.