Lee Eun-saem started her acting career as a child actress in 2007 with the KBS1 series TV Novel: Landscape in My Heart. In 2009, she appeared in the drama film Fly, Penguin. After years of hiatus to focus on her studies, she returned to the big screen in 2017 through the action-comedy movie Midnight Runners. In 2018, she joined the casts of several television dramas such as MBC’s Bad Papa and OCN’s Priest. In 2019, she played a supporting character in tvN’s Black Dog. In 2021, she acted alongside Junho and Lee Se-young in the hit MBC sageuk The Red Sleeve Cuff. In 2022, she received international recognition after becoming part of the popular Netflix zombie series All of Us Are Dead.