Latinas have lower quality of life than Caucasian cancer survivors but we know little about factors associated with quality of life in this growing population. Bilingual staff conducted interviews with a national cross-sectional sample of 264 Latina breast cancer survivors. Quality of life was measured using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Regression models evaluated associations between culture, social and medical context and overall quality of life and its subdomains. Latina survivors were 1–5 years post-diagnosis and reported a lower mean quality of life score compared to other published reports of non-Latina survivors (M = 105; SD = 19.4 on the FACT-B). Culturally based feelings of breast cancer-related stigma and shame were consistently related to lower overall quality of life and lower well-being in each quality of life domain. Social and medical contextual factors were independently related to quality of life; together cultural, social and medical context factors uniquely accounted for 62 % of the explained model variance of overall quality of life (Adjusted R2 = 0.53, P < 0.001). Similar relationships were seen for quality of life subdomains in which cultural, social, and medical contextual variables independently contributed to the overall variance of each final model: physical well-being (Adjusted R2 = 0.23, P < .001), social well-being (Adjusted R2 = 0.51, P < 0.001), emotional well-being (Adjusted R2 = 0.28, P < 0.001), functional well-being (Adjusted R2 = 0.41, P < 0.001), and additional breast concerns (Adjusted R2 = 0.40, P < 0.001). Efforts to improve Latinas’ survivorship experiences should consider cultural, social, and medical contextual factors to close existing quality of life gaps between Latinas and other survivors.