The original cast returned to voice their characters and features the guest voice of Seth MacFarlane as "I.S.R.A.E.L." (Intelligent Smart Robot Animation Eraser Lady), and Vernon Wells as the villainous Network Head. While the television series was produced and animated by Rough Draft Studios using digital ink and paint, the film was instead produced and animated by 6 Point Harness and done entirely in flash animation using Toon Boom and Adobe Flash Professional due to budget cuts.
Foxxy Love discovers that she can swear without being censored, and realizes that the TV show Drawn Together has been cancelled in favor of "The Suck My Taint Show". Foxxy calls the network to find out why they were cancelled. The Network Head, upon hearing from Foxxy, learns that the housemates are still alive and summons I.S.R.A.E.L. (Intelligent Smart Robot Animation Eraser Lady), a robot designed specifically to erase cartoon characters. Once they escape from I.S.R.A.E.L., Foxxy insists that the way for them to survive is to get their TV show back on the air. Clara, refusing to believe that she is not a real princess, claims that her father can protect them. Captain Hero, Xandir and Ling-Ling decide to go with Clara, while Spanky and Wooldoor decide to go with Foxxy to try to get their show back on the air. While the others are arguing, Toot steals a van and drives off alone. Clara, Hero, Molly (a corpse Hero believes to be his girlfriend), Xandir and Ling-Ling arrive at Clara's kingdom, expecting to find refuge. Clara encounters the king of the land, who is not her father. The guards end up dismembering and eventually killing Clara, but the other three manage to escape. Meanwhile, Foxxy, Spanky and Wooldoor visit the Suck My Taint Girl, who reveals herself to be a fan of the housemates' show. She tells the group that they were cancelled because vulgar and offensive content is only acceptable when your show "makes a point", and that if they want to get Drawn Together back on the air, they will need to get a point, which they can do by making a visit to Make-A-Point Land. The wizard of Make-A-Point Land agrees to give the group a point, and presents them with a box containing the previously mentioned point. Wooldoor opens the box to find out it contains an eraser bomb which erases him from existence. It is then that the Network Head, the Jew Producer and I.S.R.A.E.L. show up to erase the remaining cast. The Suck My Taint Girl reveals that she is the Network Head's wife. The Jew Producer manages to convince I.S.R.A.E.L. to spare the housemates, and she then impales the Network Head on a spike. The Network Head opens his coat to reveal that he had enough explosive erasers strapped to his waist to destroy all of Make-A-Point Land. The Jew Producer and the Suck My Taint Girl struggle for possession of the detonator, in the process dropping it, erasing all of Make-A-Point Land. The housemates make it out just in time with the help of The Giant Who Shits Into His Own Mouth. The housemates visit the remains of the erased Drawn Together house. The Jew Producer's son shows up to inform them that he might be able to help them by giving them a direct-to-DVD movie. I.S.R.A.E.L. arrives at the scene and she and the giant become smitten with each other. Everyone laughs happily until Spanky accidentally steps on an eraser bomb caught in the ground, which erases them all from existence, never to be seen again, therefore completing the Network Head's plan.
Jess Harnell as: Captain Hero, a chauvinistic, perverted, necrophilic, latently bisexual and lecherous parody of Superman and other superheroes, with a visual style taken from the cartoons of Bruce Timm and Max Fleischer Wile E. Coyote Rhino Guard 1 (Brian) The King Bedrock bartender Cree Summer as: Foxxy Love, a sharp-tongued ghetto parody of Valerie Brown from Hanna-Barbera's Josie and the Pussycats Suck My Taint Girl, the star of The Suck My Taint Show and a spoof of South Park characters The Network Head's wife Old Lady James Arnold Taylor as: Wooldoor Sockbat, a bizarre children's show character in the mold of SpongeBob SquarePants, who displays many of the typical reality-defying behaviors of Looney Tunes characters The Jew Producer, the person in charge of the Drawn Together show, grew attached to the characters and defended them from I.S.R.A.E.L. Road Runner Barney Rubble Eddie, the Jew Producer's Christian next-door neighbor Brainy and Hefty Smurf The Make-A-Point wizard "Suck My Taint Show" audience members Adam Carolla as Spanky Ham, a sex-obsessed, toilet-humored, obnoxious pig and a parody of Internet Flash cartoon characters Tara Strong as: Princess Clara, a pampered, fundamentalist and bigoted princess who is a parody of Disney princesses like Ariel from The Little Mermaid (1989) and Belle from Beauty and the Beast (1991) Toot Braunstein, an overweight, alcoholic and emotionally unstable sex symbol from the 1920s, reminiscent of Betty Boop Sasha, the Network Head's daughter The red-haired princess Betty Rubble Bedrock Blonde Abbey DiGregorio as Ling-Ling, a homicidal anime character based on Pikachu from the Pokémon franchise, who battles using various supernatural powers/abilities (reminiscent of anime) and speaks in pseudo-Japanese gibberish (or "Japorean", as DiGregorio calls it) with English subtitles. Jack Plotnick as Xandir P. Wifflebottom, a homosexual and effeminate parody of video-game heroes like Link from The Legend of Zelda series. Seth MacFarlane as I.S.R.A.E.L. (Intelligent Smart Robot Animation Eraser Lady), a robot deployed by the Network Head to permanently erase the entire Drawn Together gang. Vernon Wells as The Network Head, the evil head of the television network who cancelled Drawn Together and attempts to erase them by various means. Dave Jeser (uncredited) as The Giant Who Shits Into His Own Mouth / Rhino Guard 2 Matt Silverstein (uncredited) as the Jew Producer's son Kaitlyn Robrock (uncredited) as Smurfette Meryl Streep as Singing That's Pure Mike Nichols Christine Baranski as Singing That's Pure Mike Nichols/Bossom Buddies Patrick Wilson as Singing That's Pure Mike Nichols Candice Bergen as Singing That's Pure Mike Nichols Philip Seymour Hoffman as Singing That's Pure Mike Nichols Christine Ebersole as Singing Bossom Buddies