Since 2011 seven innovative drugs were commercialized for the treatment of metastatic melanoma (MM), significantly improving patient survival and management cost in 1st line of treatment. With 52% of patients now reaching a second line of treatment, the optimal sequence in patients with BRAF wild-type metastatic melanoma (MM) remains unclear. To inform policy makers about the value of these sequences, we performed a cost-effectiveness analysis comparing treatment sequences for BRAF wild-type MM in real life in France. Four sequences were compared: Anti-PD1-Ipilimumab, Ipilimumab-Anti-PD1, Ipilimumab+Nivolumab-Chemotherapies, Chemotherapies-Immunotherapies. Clinical (efficacy and utility) and economic data were extracted from the prospective MelBase cohort, collecting individual data in 1,435 MM patients from 26 French hospitals, from MM diagnosis until death. To adjust for confounding effects and differences in patient characteristics among groups, the inverse probability of treatment weighted with a propensity score (PS) for multiple treatments was used. The PS was estimated using generalized boosted modeling. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. Survival and costs were extrapolated using a multistate model, describing the 10-year course of the disease. Among the 1435 patients, effectiveness was assessed on 843 wild-type patients included between 2013 and 2019. In the base case, the 4 sequences remains on the efficiency frontier. The incremental cost-effectiveness ratio (ICER) of Anti-PD1-Ipilimumab is 136,255€ / QALY gained compared with Chemotherapies-Immunotherapies. The ICER of Ipilimumab-Anti-PD1 is 115,960€ per QALY gained compared with Anti-PD1-Ipilimumab. The ICER of Ipilimumab+Nivolumab-Chemotherapies is 806,340€ per QALY gained compared with Ipilimumab-Anti-PD1. For patients with BRAF wild-type MM, for thresholds between 0 and 800,000€, only Chemotherapies-Immunotherapies sequences has more than 55% chance of being efficient in France based on observational data.