This study examined the acculturative and psychosocial predictors of academic-related outcomes among Cambodian American high school students from an urban school district in the State of Massachusetts. Student participants (N = 163) completed an anonymous survey that assessed demographic characteristics, acculturative experiences, intergenerational conflict, depression, and academic-related outcomes. The main results indicated that acculturative and psychosocial variables were significant predictors of academic-related outcomes. Specifically, Cambodian and Anglo/White cultural orientations and depression played significant roles across the four dimensions of academic-related outcomes, including grade point average, educational aspirations, beliefs in the utility of education, and psychological sense of school membership. This study provides important implications for school-based and family-based prevention and intervention programs in addressing the acculturative and academic challenges faced by Cambodian American students.