Familism is a key cultural value that emphasizes support and attachment, loyalty, honor, and obligation to the family and is hypothesized to be critical in shaping family dynamics and individual adjustment among Hispanic/Latino individuals. To advance the field, we drew from cultural-ecological and developmental models to examine familism as a cultural promotive and risk factor for individual adjustment and family relationship quality. We conducted a systematic review and meta-analysis via a search between 2017 and 2020 and identified 126 records (23% unpublished dissertations) from 73 independent studies (12% longitudinal) in PsycINFO/Proquest, PubMed, and ERIC databases between 1993 and 2019. The multilevel meta-analysis revealed significant effects: educational outcomes, r = .16, 95% CI [.08, .23]; family relationships, which included warmth/support, r = .24, 95% CI [.19, .29], and conflict/negativity, r = −.13, 95% CI [−.23, −.02]; internalizing symptoms, r = −.12, 95% CI [−.16, −.09]; and externalizing symptoms, r = −.10, 95% CI [−.18, −.03]. We tested conceptually driven moderators and found significant variation by sample (e.g., nativity, developmental period) and context characteristics (i.e., U.S. states characterized as “established” or “new/emerging” for Hispanic/Latino populations). Findings suggest that familism may function more as a promotive and less as a risk factor and that continued attention is needed to the conditions that strengthen or weaken these associations. Although conclusions are limited because most effect sizes were from cross-sectional designs with U.S. Mexican-origin participants and relied on self-reports, findings highlight the complex associations between familism and adjustment/relationship quality and can guide future research.