Melanoma is a skin cancer with a high mortality rate due to its invasive characteristics. Currently, immunotherapy and targeted therapy increase patient survival but are ineffective in the advanced stages of the tumor. Quercetin (Que) is a natural compound that has demonstrated chemopreventive effects against different types of tumors. This review provides evidence for the therapeutic potential of Que in melanoma and identifies its main targets. The Scopus, Web of Science, and PubMed databases were searched, and studies that used free or encapsulated Que in melanoma models were included, excluding associations, analogs, and extracts. As a result, 73 articles were retrieved and their data extracted. Que has multiple cellular targets in melanoma models, and the main regulated pathways are cell death, redox metabolism, metastasis, and melanization. Que was also able to regulate important targets of signaling pathways, such as PKC, RIG-I, STAT, and P53. In murine models, treatment with Que reduced tumor growth and weight, and decreased metastatic nodules and angiogenic vasculature. Several studies have incorporated Que into carriers, demonstrating improved efficacy and delivery to tumors. Thus, Que is a promising therapeutic agent for the treatment of melanoma; however, further studies are needed to evaluate its effectiveness in clinical trials.