Introduction: A home-based, low-intensity physical activity program (Onco-Move) and a supervised, moderate-to-high intensity, combined resistance and aerobic exercise program (OnTrack) have proven to be effective in maintaining physical fitness and reducing fatigue among breast cancer patients undergoing adjuvant chemotherapy. This study evaluated the cost–utility and cost-effectiveness of Onco-Move and OnTrack. Methods: A total of 230 patients were randomized to Onco-Move, OnTrack, or usual care (UC). Health outcomes included quality-adjusted life years (QALYs), general and physical fatigue, and physical fitness measured at baseline, end of chemotherapy, and 6-month follow-up. Societal costs included professional and informal health care, work absenteeism, and unpaid productivity costs. Cost data were based on 3-monthly questionnaires, supplemented by medication data obtained from pharmacies. Results: Onco-Move is not likely to be cost-effective due to the relatively high willingness-to-pay necessary to reach reasonable probabilities of cost-effectiveness (QALY, general and physical fatigue). Incremental cost-effectiveness ratios for OnTrack compared to UC were €26,916/QALY, €788/1-point decrease in general fatigue and €1402/1-point decrease in physical fatigue. The probability of OnTrack being cost-effective ranged from 31% at a willingness-to-pay (WTP) of €0–79% at a WTP of €80,000/QALY, 97% at a WTP of €15,000/1-point decrease in general fatigue, and 86% at a WTP of €24,000/1-point decrease in physical fatigue. Both interventions had a low probability of being cost-effective for physical fitness. The probability of cost-effectiveness for both interventions was greater among compliant participants. Conclusions: Onco-Move is not likely to be cost-effective. Depending on the decision-makers’ willingness-to-pay, OnTrack could be considered cost-effective in comparison with UC. Trial registration Clinical trial registration number of the Netherlands Trial Register—NTR2159.