After Stan is told that he is the reincarnation of L. Ron Hubbard, he goes into his room to find Tom Cruise sycophantically waiting for him. Assuming that Stan will recognize him as Hubbard's most loyal follower, Tom asks him if he approves of his acting. Stan however tells him he is only OK - not as good as Leonardo DiCaprio, or Gene Hackman or the guy who played Napoleon Dynamite - causing Tom to break down into hysterics, and locks himself in Stan's closet.
He remains there for the majority of the episode, refusing to "come out of the closet" despite the attempts made by Stan, Randy Marsh, the police and even his ex-wife Nicole Kidman, all of whom assure him it's time for him to come out of the closet and that no one would judge him for doing it. He continues to refuse to leave the closet and at times, even refuses to acknowledge that he is indeed physically inside a closet, causing Nicole to respond "Then how am I talking to you Tom?"
When Stan turns against the teaching of Scientology, informing its followers that it's all just a big scam created to get money, Cruise, Travolta and Kelly at last come out of Stan's closet. Cruise, Travolta and the rest of the Scientologists present begin yelling furiously at Stan for insulting their religion and that they all intend to sue him for slander. This angers Stan enough to start yelling back to go ahead and sue him.
Tom Cruise has carried out his threat against Stan in the 200th Episode, when Stan along with Kyle, Butters, and Mr. Garrison insult Cruise (again), by calling him a "fudge packer" (when he is physically in a fudge factory and loading fudge into boxes), Cruise becomes infuriated, instead claiming that he is "fly fishing". He becomes so infuriated that he calls together every Celebrity that South Park has ever offended, in going together on a class action lawsuit against the town.
His real plan however is not to sue the town, but rather get South Park to locate and deliver to them the Muslim Prophet, Muhammad, whose inner-goo makes him immune to ridicule. When a group of Gingers threaten violence so they can get the goo, Cruise and the celebrities activate a newly rebuilt Mecha-Streisand to destroy South Park.
In the second part episode, "201", after the gingers captured Muhammad, they agreed to let the celebrities have some of the goo in exchange for the gingers being allowed to use Rob Reiner's machine. Some of Muhammad's goo was transferred into Cruise, and he was censored. Later, when the celebrities were fighting the Super Best Friends, Seaman jumped onto his back, and everyone made jokes about him having semen on his back. Cruise's censor disappeared, but the explanation as to why this happened was censored (It was really because that only terrorizing works). After he lost, Stan once again apologized to Cruise for calling him a fudge packer and saying that Seaman is on his back, and then he, Kyle, Cartman, and Kenny sent him to the moon where they still believed that's where the Zypods lived as seen in "Free Willzyx" where Cruise suffocated to death on the moon. Cruise and the whale then make a cameo in "Coon 2: Hindsight" when DP is drilling on the moon.
Despite suffocating to death on the moon in his previous appearance, he somehow reappears in Stan's closet when you try to open it. He doesn't make a physical appearance, however, but his voice is heard saying "I'm never coming out!", a reference to "Trapped in the Closet".
Tom Cruise is depicted as a relatively faithful representation of his real-life self, with brown hair and slight stubble.
In "Trapped in the Closet", Tom Cruise is wearing a black suit with a striped blue shirt underneath.
In "200", Tom Cruise also wears a fudge packing uniform while working at a fudge factory.
- Cruise's home is shown to have hundreds of closets, again referencing rumors about him being gay.
- In "200", Stan sees Tom Cruise working in a candy factory, packaging fudge into boxes for distribution and proceeds to call him a "fudge packer". This, like "come out of the closet", is another reference to the gay rumors about Cruise.
- Although Tom Cruise is currently married to actress Katie Holmes, his ex-wife Nicole Kidman was instead selected for the episode to coax Tom out of the closet, despite that fact Nicole Kidman is not a practicing Scientologist. Holmes herself has not appeared in the series despite her husband's four appearances.
- Tom Cruise's hysterical behavior is in a parody of his publicized behavior such as the jumping on the couch incident during a segment on the Oprah Winfrey Show and his heated argument with Matt Lauer in regards to prescription drugs on the Today Show.
- When Tom Cruise gets sent to the moon in "201", he is seen lying next to Jambu (or Willzyx), the whale that the boys sent to the moon in the Season Nine episode "Free Willzyx", after being tricked by sea park employees.