Objective: To assess the potential cost-effectiveness of prehabilitation in medically frail patients undergoing surgery for epithelial ovarian cancer (EOC). Methods: We created a cost-effectiveness model evaluating the impact of prehabilitation on a cohort of medically frail women undergoing primary surgical intervention for EOC. Cost was assessed from the healthcare system perspective via (1) inpatient charges from 2018–2019 institutional Diagnostic Related Grouping data for surgeries with and without major complications; (2) nursing facility costs from published market surveys. Major complication and non-home discharge rates were estimated from the literature. Based on published pilot studies, prehabilitation was determined to decrease these rates. Incremental cost-effectiveness ratio for cost per life year saved utilized a willingness-to-pay threshold of $100,000/life year. Modeling was performed with TreeAge software. Results: In a cohort of 4,415 women, prehabilitation would cost $371.1 Million (M) versus $404.9 M for usual care, a cost saving of $33.8 M/year. Cost of care per patient with prehabilitation was $84,053; usual care was $91,713. When analyzed for cost-effectiveness, usual care was dominated by prehabilitation, indicating prehabilitation was associated with both increased effectiveness and decreased cost compared with usual care. Sensitivity analysis showed prehabilitation was more cost effective up to a cost of intervention of $9,418/patient. Conclusion Prehabilitation appears to be a cost-saving method to decrease healthcare system costs via two improved outcomes: lower complication rates and decreased care facility requirements. It represents a novel strategy to optimize healthcare efficiency. Prospective studies should be performed to better characterize these interventions in medically frail patients with EOC.