A marketing infomercial informs us about how to take advantage of the power of Space Ghost. Mock behind-the-scenes glimpses at the making of a Space Ghost episode, as well as footage of future Space Ghost episodes are also shown. After the infomercial, the actual Space Ghost: Coast to Coast episode starts, which merely consists of the winners of the "Haiku'n for Space Ghost" contest, Ryah Rosenberg and Sean Medlock, reading their entries.

Space Ghost reveals that he's dying. At the end of the episode, Space Ghost announces that it's time for him to die. He keels over and lays on the floor for several seconds before opening his eyes and realizing that as a ghost, he's already dead, so it isn't so bad.

Space Ghost decides to put the moves on guest Merrill Markoe, with help from guest Adam Carolla. However, all advice backfires and Merrill ends up disgusted with Space Ghost. Zorak successfully flirts with Merrill, and when Space Ghost catches Zorak doing so, they violently settle their differences on The Jerry Springer Show.

Space Ghost is handed a lawsuit by his former sidekicks, Jan and Jace, for withholding rerun profits from them, among other things. Space Ghost enlists the help of Greta Van Susteren in his case. The lawsuit is thrown out when Jan and Jace's lawyer, Dr. Nightmare, is revealed to be Ted Turner's son.

A major storm is headed for the Ghost Planet. However, it's eventually revealed that the storm is actually a carnival. Garrett Morris and Mark McEwen are interviewed.

Space Ghost watches "The Warren Show" and notices he's the guest being interviewed by Warren. Space Ghost never remembers being a guest on Warren's show, so he, Moltar, and Zorak travel to Warren's cave to inquire on the situation. Upon arrival, Space Ghost discovers that the replicant who was on "The Warren Show" is named Gary, a nod to the original Space Ghost actor Gary Owens. Space Ghost destroys Gary. Warren is furious but gets even by stealing Space Ghost's show. Space Ghost destroys Warren in retaliation.

Space Ghost replaces Moltar (who was traded to a Japanese baseball team) with a live action dog named Rags. When Rags proves incompetent, Space Ghost goes to Japan to get Moltar back.

Space Ghost writes a screenplay and interviews guests Ben Stiller, Kevin Smith, and Jim Jarmusch as potential candidates to direct his movie. In the end, Space Ghost decides to direct the movie himself.

A live action intern, Joey, is a nuisance on the set. Eventually, Space Ghost gets fed up with Joey's disruptions and blasts him.

During a battle with Future Man, Space Ghost is sprayed with a gas that causes him to crave human flesh. Back at the studio, Space Ghost interviews guests Moby and Emo Phillips, but eats both of them before the interview is up. Space Ghost also eats Zorak and Moltar while guest Shirley Manson looks on. It turns out the whole episode was a dream by Kirk the Storyteller.

Space Ghost decides that the Ghost Planet is moving to America, and he gets into the American spirit. However, the Ghost Planet actually touches down in Mexico instead.

Space Ghost interviews Denis Leary. Meanwhile, Moltar is going to destroy the planet in seven minutes, while also having an "everything must go" sale. Space Ghost forgets to stop the planet destruction and the studio explodes. Later, at camp, Space Ghost, standing in front of some kids, wraps up a story about how he saved Christmas, and orders them to get back to work.