Connie (NIA VARDALOS) and Carla (TONI COLLETTE) are two life-long friends who've always shared their love of performing old show tunes. They've persevered doing so despite earlier peer criticism and having few fans, such is what they now get playing the waiting lounge at their local airport.
When they witness a local businessman, Rudy (ROBERT JOHN BURKE), kill their boss over a drug deal gone bad, however, the two women leave their boyfriends -- Al (NICK SANDOW) and Mikey (DASH MIHOK) -- and literally take their show on the road, unaware that they're carrying a kilo of Rudy's cocaine. Realizing that Rudy and his goon, Tibor (BORIS MCGIVER), will likely look for them in dinner theaters and other such venues, the two decide to travel to the place they think that's lacking in culture, Los Angeles.
Once there, they stumble across an audition for a drag queen show and figure they can kill two birds with one stone if they get the job. Not only will they be incognito as women masquerading as men dressed like cross-dressers, but they'll also get to perform on stage. When the two sing during their audition, they impress club owner Stanley (IAN GOMEZ) enough that he immediately hires them.
The two slowly but surely become popular among the gay and cross-dressing population, eventually drawing the attention of fellow cross-dressers Robert (STEPHEN SPINELLA), Lee (ALEC MAPA), Brian (CHRISTOPHER LOGAN) and Paul (ROBERT KAISER) who all want in on Connie and Carla's show.
Despite the latter worrying that their growing fame might be drawing too much attention to themselves, especially when they use their real names for their act, the two begin to enjoy their new lives. Yet, as Rudy and Tibor eventually close in on them, and Connie falls for Michael's estranged brother, Jeff (DAVID DUCHOVNY), who thinks she's really a he playing a she, the two are unsure how long they can carry on their ruse.