Kusama currently serves as an executive producer on the Showtime survival horror thriller series Yellowjackets (2021–present), for which she was nominated for two Primetime Emmy Awards.

[9] Her jobs before making it big in the film industry varied from nannying, house painting, editing, and working with the production of independent films/ music videos.

[10] In 1992, after partnering with John Sayles as an assistant, she joined Gleason's Gym in Dumbo, Brooklyn where she started boxing.

In 2005, Kusama directed her second film, Æon Flux, a Paramount Pictures studio production that starred Charlize Theron and had a budget of US$62,000,000.

[14] The film was largely panned by critics and grossed $52 million worldwide,[17] putting Kusama's career on ice for years afterwards.

[18] In 2009, Kusama directed the horror film Jennifer's Body, which was written by Diablo Cody and starred Megan Fox and Amanda Seyfried in the lead roles.

Starting in 2014, Kusama began working regularly in television as a director on several series, such as Halt and Catch Fire, The Man in the High Castle, Casual, Billions, and The Outsider.

Kusama was slated to direct an adaptation of Breed, an adult horror novel by Scott Spencer under the pen name Chase Novak.

[25] In 2015, Kusama directed The Invitation, a horror film written by Hay and Manfredi, and starring Logan Marshall-Green.

[34][35] In 2018, Kusama directed the crime drama film Destroyer, which starred Nicole Kidman and Tatiana Maslany.

[38][39][40][41] In 2020, a new Dracula film was announced as in development by Blumhouse Productions, featuring Kusama as director and Phil Hay and Matt Manfredi as writers.

[43] Kusama's films have been noted for their strong feminist themes, and with the exception of The Invitation, all have featured female protagonists.

In addition to themes of feminism, Kusama takes the time to investigate and understand the darker side of psychology for her characters.

With Destroyer, she aimed to authentically depict parts of the city not often seen in popular culture, resulting in its location shooting going "off the beaten path."

Since she has a dark overall theme for her films, many of her works have dim and darkened lights in terms of color and most of her tones are way below the audible ranges of her landscapes so in the final project they come off as vibratory in theater.

Ensuring she has a controlled aesthetic, she uses isolation techniques, dead spaces, and the camera to create personal feelings with her characters.

[48] Kusama was initially inspired to make films–particularly centered around women–by her viewings of Amy Heckerling's Fast Times at Ridgemont High (1982) as well as Martha Coolidge's Valley Girl (1983).