INTRODUCTION: Skin cutaneous melanoma (SKCM) is a common malignant skin cancer with high mortality and recurrence rates. Although the mRNA vaccine is a promising strategy for cancer treatment, its application against SKCM remains confusing. In this study, we employed computational bioinformatics analysis to explore SKCM-associated antigens for an mRNA vaccine and suitable populations for vaccination. METHODS: Gene expression and clinical data were retrieved from GEO and TCGA. The differential expression levels and prognostic index of selected antigens were computed via GEPIA2,while genetic alterations were analyzed using cBioPortal. TIMER was utilized to assess the correlation between antigen-presenting cell infiltration and antigen. Consensus clustering identified immune subtypes, and immune characteristics were evaluated across subtypes. Weighted gene co-expression network analysis was performed to identify modules of immune-related genes. RESULTS: We discovered five tumor antigens (P2RY6, PLA2G2D, RBM47, SEL1L3, and SPIB) that are significantly increased and mutated, which correlate with the survival of patients and the presence of immune cells that present these antigens. Our analysis revealed two distinct immune subtypes among the SKCM samples. Immune subtype 1 was associated with poorer clinical outcomes and exhibited low levels of immune activity, characterized by fewer mutations and lower immune cell infiltration. In contrast, immune subtype 2 showed higher immune activity and better patient outcomes. Subsequently, the immune landscape of SKCM exhibited immune heterogeneity among patients, and a key gene module that is enriched in immune-related pathways was identified. CONCLUSIONS: Our findings suggest that the identified tumor antigens could serve as valuable targets for developing mRNA vaccines against SKCM, particularly for patients in immune subtype 1. This research provides valuable insights into personalized immunotherapy approaches for this challenging cancer and highlights the advantages of bioinformatics in identifying immune targets and optimizing treatment approaches.