After completing her studies, Russo-Otstot began her career as a writer. She sold a pilot to HBO when she was 25 years old, and went on to write for FX's The Shield and ABC's V. She also taught screenwriting and playwriting at Case Western Reserve University and the Cleveland Institute of Art. During that time, her brothers recruited her to join AGBO. In 2017, she joined AGBO as senior vice president of the story department under Christopher Markus and Stephen McFeely, and developed Netflix's Extraction and A24's Everything Everywhere All At Once, which won seven Academy Awards, including Best Picture. Along with Jessica Goldberg, she co-wrote Apple TV+'s , which was released in early 2021. In November 2022, she was promoted from president of creative to chief creative officer at AGBO. She was an executive producer for The Gray Man (Netflix, 2022), Citadel (Amazon Prime Video, 2023), Extraction 2 (Netflix, 2023), and The Electric State (Netflix, 2025). She is one of the producers of the upcoming Netflix film , set to star Robert De Niro.