Ashley is a journalist and does makeovers for a TV show. Her editor offers her the job of being the editor of a new fashion supplement, provided she does a makeover on a sports writer, who is an uncouth, loudmouthed, sexist slob.

Tweek City is a week in the life of Bill, a potentially closeted, half-Latino, small-time speed dealer in San Francisco's Mission District. Bill is stuck on an endless walk from one empty experience to the next. Only Bill's friend Jerm has the ability to connect and ground him in reality. When Jerm makes an ill-advised stage dive, Bill plunges into a downward spiral that takes him on a nocturnal journey through the streets of San Francisco and ultimately down to Los Angeles where he crashes his high school sweetheart's wedding. From his sleep-deprived, hallucinogenic state, Bill fails miserably in a desperate attempt to reconnect with his first and only love. With nowhere else to go, Bill jacks a car and ends up at the deserted drive-in theater of his childhood where he is forced to confront the ghosts that he had tried to leave behind.

In Los Angeles at the turn of the 1970s, drug-fueled detective Larry "Doc" Sportello investigates the disappearance of an ex-girlfriend.