U.S. born Latina/o adolescents have a disproportionately higher lifetime prevalence of mental health disorders, higher rates of school dropout, and score lower on academic achievement measures when compared to their Non-Latina/o, White or Asian peers. Given the substantial exposure to risk factors, identifying and understanding salient sources of resilience is essential to promoting and enhancing positive adjustment among Latina/o youth. Familism is a cultural value embraced by many Latina/os that has been associated with positive academic and psychosocial outcomes for Latina/os adolescents. When measured, familism commonly includes dimensions of obligation, support and family as referent. Previous studies have indicated that dimensions of familism, such as obligation and support, may differentially predict psychological well-being and academic achievement. No published studies to date have examined the differential relationships of the constructs of familism obligation and familism support values explicitly as separate predictors in the contexts of both mental health and academic achievement for Latina/o youth. The primary purpose of this quantitative study was to examine the differential predictive relationships of familism support and familism obligation values on mental health and academic achievement of Latina/o adolescents. A secondary purpose was to examine the potential moderating or mediating roles of family functioning and gender on these pathways. This study is consistent with the Cultural Ecological Transactional Theory of Resilience as a framework for describing how multiple factors may contribute to risk or resilience of Latino youth. Participants were 36 Latina/o youth between the ages of 11-15 years old in a Central Texas middle school. Results found evidence for the moderating role of family distress on the relationship between familism obligation values and GPA among both male and female Latino adolescents. Implications, limitations and areas for further research are discussed.