Purpose: This study assessed the effects of 12-week supervised resistance training combined with home-based physical activity on physical fitness, cancer-related fatigue, depressive symptoms, health-related quality of life (HRQoL), and life satisfaction in female breast cancer survivors. Methods: A parallel-group, outcome assessor-blinded, randomized controlled trial included 60 female breast cancer survivors who had completed their core treatments within the previous 10 years. Through computer-generated simple randomization, participants were assigned to resistance training (RTG; two sessions/week for 12 weeks plus instructions to undertake ≥ 10,000 steps/d) or control (CG; ≥ 10,000 steps/d only). Outcomes were evaluated at baseline and week 12. Muscular strength was assessed with electromechanical dynamometry. A standardized full-body muscular strength score was the primary outcome. Secondary outcomes included cardiorespiratory fitness, shoulder mobility, cancer-related fatigue, depressive symptoms, HRQoL, and life satisfaction. Results: Thirty-two participants were assigned to RTG (29 achieved ≥ 75% attendance) and 28 to CG (all completed the trial). Intention-to-treat analyses revealed that the standardized full-body muscular strength score increased significantly in the RTG compared to the CG (0.718; 95% CI 0.361–1.074, P < 0.001, Cohen's d = 1.04). This increase was consistent for the standardized scores of upper-body (0.727; 95% CI 0.294–1.160, P = 0.001, d = 0.87) and lower-body (0.709; 95% CI 0.324–1.094, P = 0.001, d = 0.96) strength. There was no effect on cardiorespiratory fitness, shoulder flexion, cancer-related fatigue, depressive symptoms, HRQoL, or life satisfaction. The sensitivity analyses confirmed these results. Conclusion: and implication for cancer survivors. In female breast cancer survivors who had completed their core treatments within the past 10 years, adding two weekly sessions of supervised resistance training to a prescription of home-based physical activity for 12 weeks produced a large increase in upper-, lower-, and full-body muscular strength, while other fitness components and patient-reported outcomes did not improve. Trial registration number. ISRCTN14601208.