Purpose Many breast cancer patients experience (severe) menopausal symptoms after an early onset of menopause caused by cancer treatment. The aim of this study was to assess the cost-effectiveness of cognitive behavioral therapy (CBT) and physical exercise (PE), compared to a waiting list control group (WLC). Methods We performed a cost-effectiveness analysis from a healthcare system perspective, using a Markov model. Effectiveness data came from a recent randomized controlled trial that evaluated the efficacy of CBT and PE. Cost data were obtained from relevant Dutch sources. Outcome measures were incremental treatment costs (ITCs) per patient with a clinically relevant improvement on a measure of endocrine symptoms, the Functional Assessment of Cancer Therapy questionnaire (FACT-ES), and on a measure of hot flushes, the Hot Flush Rating Scale (HFRS), and costs per quality-adjusted life years (QALY) gained over a 5-year time period. Results ITCs for achieving a clinically relevant decline on the FACT-ES for one patient were €1,051 for CBT and €1,315 for PE, compared to the WLC. The corresponding value for the HFRS was €1,067 for CBT, while PE was not more effective than the WLC. Incremental cost-utility ratios were €22,502/QALY for CBT and €28,078/QALY for PE. Conclusion CBT is likely the most cost-effective strategy for alleviating treatment-induced menopausal symptoms in this population, followed by PE. The outcomes are sensitive to a reduction of the assumed duration of the treatment effect from 5 to 3 and 1.5 years. Implications for Cancer Survivors Patients can be prescribed CBT or, based on individual preferences, PE.