Purpose: This study explored the relationships between systemic- and individual-level contextual factors and health-related quality of life (HRQOL) in a cohort of African American and Latina breast cancer survivors (BCS)., Methods: Baseline questionnaire data of 320 BCS who participated in a HRQOL psycho-educational intervention were abstracted from the parent study. Hierarchical regression analysis tested the independent effects of contextual factors on HRQOL., Results: HRQOL was higher in BCS who: were diagnosed at < stage 2 (b = -1.38, p < 0.05), expressed satisfaction with their health care (b = 0.20, p < 0.001), had fewer comorbidities (b = - 0.60, p < 0.001) and depressive symptoms (b = -0.30, p < 0.001), and practiced healthy diet and exercise habits (b = 0.02, p < 0.05). Demographic and cancer-related factors accounted for 14 % of the variance in HRQOL (F[6, 274] = 7.25, p < 0.001). The socio-cultural context (i.e., ethnicity, life stress, perceived social support) explained 20 % of the variance in HRQOL (FΔ[3, 271] = 27.32, p < 0.001). The health care system context contributed an additional 8 % to explaining HRQOL (FΔ[1, 270] = 34.88, p < 0.001). Health status and behavioral factors accounted for 18 % of the variance (FΔ[4, 266] = 29.55, p < 0.001). The full model explained 59 % of the variance in HRQOL (F[14, 266] = 27.76, p < 0.001)., Conclusions: HRQOL in ethnic minority BCS is multifaceted and is significantly influenced by cancer-related, socio-cultural, health care system, health status, and behavioral contextual factors. Therefore, survivorship research and practice must address broad multi-level domains to achieve equitable and optimal breast cancer outcomes., Implications for Cancer Survivors: To enhance HRQOL, survivors must be provided the know-how and support to maintain healthy lifestyle and self-management practices. Advocates must engage the care team to consider systemic factors, including life stress and community resources, to be more patient-centered.