Cancer is a leading cause of death in the U.S., significantly affecting adolescents, particularly those from racial/ethnic minority backgrounds, rural areas, or lower socioeconomic groups who face higher cancer rates and poorer outcomes. Unhealthy lifestyle choices, including tobacco and alcohol use, poor diet, lack of exercise, and unprotected sun exposure, contribute to nearly half of adolescent cancer diagnoses. However, a knowledge gap persists among youth regarding their susceptibility to cancer, highlighting the need for effective prevention education tailored to them. Leveraging adolescents’ engagement with digital technology, a well-designed serious game could foster awareness and promote healthy behaviors, addressing a gap in U.S. school-based cancer prevention programs and helping vulnerable adolescents reduce their future cancer risks.