Background: Recent findings from the PEACE-1 and ARASENS trials have demonstrated survival benefits in men with newly diagnosed metastatic hormone-sensitive prostate cancer using different triplet therapies, including Abiraterone and Darolutamide added to Androgen Deprivation Therapy and Docetaxel. Given the rising costs of cancer care, this study aimed to assess the cost-effectiveness of these treatment regimens. Methods: Drug prices were obtained from drugs.com and assurance-maladie.ameli.fr at wholesale prices to evaluate both United States (US) and France payer perspectives. Survival and progression data were sourced from Kaplan-Meier curves of the PEACE-1 and ARASENS trials and fitted to Weibull distribution models in R. The parameters were imported into TreeAge Pro 2023 for partitioned survival analysis. Health states were classified as "Pre-Progression,""Post-Progression," and "Death," each assigned specific health utility values and costs. Outcomes including total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Uncertainty was addressed through one-way and probabilistic sensitivity analyses. The baseline willingness-to-pay (WTP) threshold was $100,000 per QALY. Euros were converted to US Dollars. Results: At the baseline WTP of 100,000, generic Abiraterone (US, France) in PEACE-1 and Darolutamide in ARASENS from the French perspective were cost-effective. Generic Abiraterone was dominant, associated with lower net costs (-1,347 to -333) and higher QALYs (0.16) and Darolutamide had an ICER of .7,001 per QALY. In contrast, other triplet therapies increased both net costs and QALYs. Abiraterone yielded ICERs of 408,074 (US) and 114,995 (France) per QALY. Darolutamide in the US had an ICER of $383,732 per QALY. On one-way sensitivity analyses, most drugs would need to be priced at less than ~4,000 a month to be cost-effective at WTP of 100,000 per QALY. On probabilistic sensitivity analyses, with WTP of 100,000 per QALY, generic Abiraterone (US) was the cost-effective drug (88% of simulations), while brand Abiraterone and Darolutamide (US) were the least cost-effective (0% of simulations). Conclusions: Cost-effectiveness of therapies in metastatic hormone-sensitive prostate cancer vary significantly based on pricing and country payer perspective. At a WTP threshold of $100,000, only generic Abiraterone (US, FRA) and Darolutamide (France) were cost-effective.