PURPOSE: It is a clinical challenge to select patients for BRAF-targeted therapy because of the lack of predictive biomarkers besides the BRAF V600E mutation. By analyzing the genome, transcriptome, and proteome, this study investigated the association between baseline molecular alterations and outcomes of BRAF-targeted therapy. PATIENTS AND METHODS: Fresh tumor tissue from patients enrolled in the Copenhagen Prospective Personalized Oncology study was collected and underwent comprehensive molecular profiling. CONCLUSION: Using a multiomic approach, we identified molecular alterations associated with treatment outcomes. The potential of analyzing multiomic data is promising and should be prioritized in translational cancer research to uncover the full potential within precision oncology.