Moon has appeared in eleven of Zombie's solo music videos and an additional four previous to that when he fronted White Zombie. She most famously starred in the Cabinet of Dr. Caligari-themed music video "Living Dead Girl". Moon appeared on the cover of the single for "Living Dead Girl" (1998), Zombie's remix album American Made Music to Strip By (1999), and the cover of the single for "Demon Speeding". Aside from Zombie's work, she also appeared in Black Label Society's video for "Stillborn" and Prong's video for "Rude Awakening". In 2003, Moon co-starred in her husband's first feature film, House of 1000 Corpses, as Vera-Ellen "Baby" Firefly, but previous to that, she claims that she had never had aspirations of becoming an Actress. As Moon explains her character in that film, "Baby is the angelic-looking bait to get the victims." Moon starred alongside genre actors Sid Haig, Bill Moseley and Karen Black. In 2004, she had a brief appearance in the Tobe Hooper film Toolbox Murders starring Angela Bettis, the only film she has been in not directed by Zombie.
On October 31, 2002 she married heavy metal musician and film Director Rob Zombie after almost nine years of dating.
Moon reprised her role as Baby Firefly in the 2005 sequel to House of 1000 Corpses, titled The Devil's Rejects. The Devil's Rejects was financially successful, recouping its roughly $7 million budget during its opening weekend, going on to earn over $16 million and better received by critics than its predecessor. Critic Roger Ebert gave the film three out of a possible four stars. Ebert wrote, "If you are a hardened horror-movie fan capable of appreciating skill and wit in the Service of the deliberately disgusting, 'The Devil's Rejects' may exercise a certain strange charm." Moon was awarded Spike TV's Scream Awards award for "Most Vile Villain" alongside co-stars Haig, Moseley and Leslie Easterbrook for their portrayal of the Firefly family. Following that, she was awarded a Fuse/Fangoria Chainsaw Award for best duo with her co-star Moseley.
Moon designed a clothing line, Total Skull, which debuted at the end of May 2006. She explains, "The phrase 'total skull' to me means awesome, rad, the best of the best."
In 2007, Moon starred as Eva Krupp in a short faux trailer segment for the film Grindhouse, directed by Zombie and titled Werewolf Women of the SS. She also appeared in her husband's remake of the 1978 classic Halloween, portraying Deborah Myers, the mother of Michael Myers and Laurie Strode. It currently stands as the highest grossing overall film in the Halloween franchise. Moon reprised her character in the sequel Halloween II, which was released on August 28, 2009. Moon provides the voice for the character of Suzi-X in the animated film The Haunted World of El Superbeasto, written and produced by her husband, Zombie. In 2010, she guest-starred on the series CSI: Miami in the episode "L.A.", which was directed by her husband.