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While advances in the understanding of tumor biology through multi-omics profiling hold the promise of substantially improving patient outcomes, the cost implications of such strategies remain unclear. We therefore performed a comparative cost analysis of patients treated either within the Tumor Profiler (TuPro) melanoma project or from a control cohort who received treatment after standard next-generation sequencing testing. After adjustment of cohorts through inverse probability of treatment weighting, we found no evidence of statistically significant differences in total costs between the two cohorts (95% confidence interval -10% to +67%). Importantly, treatment costs (95% confidence interval -28% to +41%) were similar between the two cohorts. In conclusion, we found no evidence that treatment recommendations guided by advanced multi-omics profiling led to significantly higher treatment costs in a Swiss context.