Melanoma is an especially fatal neoplasm resistant to traditional treatment. The advancement of novel therapeutical approaches has gained attention in recent years by shedding light on the molecular mechanisms of melanoma tumorigenesis and their powerful interplay with the immune system. The presence of many mutations in melanoma cells results in the production of a varied array of antigens. These antigens can be recognized by the immune system, thereby enabling it to distinguish between tumors and healthy cells. In the context of peptide cancer vaccines, generally, they are designed based on tumor antigens that stimulate immunity through antigen-presenting cells (APCs). As naked peptides often have low potential in eliciting a desirable immune reaction, immunization with such compounds usually necessitates adjuvants and nanocarriers. Actually, nanoparticles (NPs) can provide a robust immune response to peptide-based melanoma vaccines. They improve the directing of peptide vaccines to APCs and induce the secretion of cytokines to get maximum immune response. This review provides an overview of the current knowledge of the utilization of nanotechnology in peptide vaccines emphasizing melanoma, as well as highlights the significance of physicochemical properties in determining the fate of these nanovaccines in vivo, including their drainage to lymph nodes, cellular uptake, and influence on immune responses.