<p>The treatment landscape for melanoma has been dramatically transformed by the advent of novel therapeutic approaches, particularly immune checkpoint inhibitors (ICIs) and targeted therapies (TTs). Clinical outcomes, such as overall survival, progression-free survival, objective response rate, and the incidence of immune-related adverse events, are useful metrics for evaluating these agents; however, cost considerations have become increasingly important. Globally, the medical costs associated with melanoma treatment are increasing. In recent years, the cost-effectiveness of ICIs and TTs in both unresectable and adjuvant settings has been extensively analyzed. Most studies have reported that anti-PD-1 antibody monotherapy is more cost-effective than combination regimens involving ICIs or TTs in both settings. However, most cost-effectiveness analyses were based on simulation models derived from international clinical trials data; therefore, they may not accurately reflect real-world outcomes, which can vary significantly among different patient populations. Furthermore, treatment costs vary substantially among countries due to differences in healthcare systems, reimbursement policies, and pricing. Cost-effectiveness analyses based on real-world data from individual countries are essential to accurately determine the most cost-effective treatment options for patients with melanoma.</p>