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Objectives: Breast cancer affects millions of women worldwide, including Indonesia and brings a burden on many aspects, especially quality of life. This study investigated the influence of demographic characteristics, psychological distress and physical activity levels on quality of life among breast cancer women undergoing therapy in Indonesia. Materials and Methods: This cross-sectional study was conducted among 200 breast cancer women. We used the Indonesian version of depression, anxiety, stress scales, international physical activity questionnaires and World Health Organization Quality of Life-BREF to evaluate psychological distress, physical activity levels and quality of life. Descriptive, bivariate and multiple linear regressions were applied. Results: Study participants had moderate quality of life scores. Approximately 22% of the variance in physical health was explained by family history, depression and physical activity. Having a family history is associated with better psychological health (ß = 5.32, P = 0.04). In contrast, experienced moderate to severe depressive symptoms contributed to lower environment domains (ß = −6.30, P = 0.02). Furthermore, having a low level of physical activity was the only significant factor influencing all domain scores, including physical health (β = −24.82, P < 0.001), psychological health (β = −19.72, P < 0.001), social relation (β = −16.91, P < 0.001) and environment (β = −13.91, P < 0.001). Conclusion: Physical activity levels are the strongest determinant of quality of life among breast cancer women in Indonesia. Nurses should not only widen information access regarding breast cancer, especially for patients with genetic risk, but also should early screen for depressive symptoms and develop strategies to motivate patients to increase their physical activity to escalate breast cancer patient's quality of life. [ABSTRACT FROM AUTHOR]