The Cancer Genome Atlas (TCGA) Network has characterized 333 primary and/or metastatic cutaneous melanomas through DNA, RNA, and protein-based analysis. The study establishes a genomic classification framework into four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant *BRAF*, mutant *RAS*, mutant *NF1*, and Triple-WT (wild-type). Integrative analysis reveals that the Triple-WT subtype is enriched for *KIT* mutations, focal amplifications, and complex structural rearrangements. No significant outcome correlation was found with genomic classification, but samples assigned to the transcriptomic "immune" subclass, characterized by high expression of immune-related genes, showed improved patient survival. This suggests that tumor stroma immunobiology influences the prognosis of melanoma patients with regional metastases, offering insights for personalized therapeutic decision-making.The Cancer Genome Atlas (TCGA) Network has characterized 333 primary and/or metastatic cutaneous melanomas through DNA, RNA, and protein-based analysis. The study establishes a genomic classification framework into four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant *BRAF*, mutant *RAS*, mutant *NF1*, and Triple-WT (wild-type). Integrative analysis reveals that the Triple-WT subtype is enriched for *KIT* mutations, focal amplifications, and complex structural rearrangements. No significant outcome correlation was found with genomic classification, but samples assigned to the transcriptomic "immune" subclass, characterized by high expression of immune-related genes, showed improved patient survival. This suggests that tumor stroma immunobiology influences the prognosis of melanoma patients with regional metastases, offering insights for personalized therapeutic decision-making.