She received critical acclaim for her dual role as Joy Wang and Jobu Tupaki in the film Everything Everywhere All at Once (2022), which earned her a nomination for the Academy Award for Best Supporting Actress.

Meanwhile, Hsu originated the main character of Christine Canigula in the first performance of Be More Chill at the regional Two River Theater in Red Bank, New Jersey.

In 2019, Hsu joined the recurring cast of the Amazon Prime series The Marvelous Mrs. Maisel for its third season as Mei Lin.

Her breakthrough role came in 2022 when Hsu co-starred as Joy Wang, the depressed daughter of Michelle Yeoh's character, and as the nihilistic antagonist Jobu Tupaki in A24's absurdist comedy-drama film Everything Everywhere All at Once.

Hsu guest starred in the "Escape from Shit Mountain" episode of the first season of Peacock series Poker Face which was released in 2023.

She also appeared in Disney+'s American Born Chinese, reuniting with fellow Everything Everywhere All at Once costars Yeoh, Ke Huy Quan, and James Hong.