<p>Melanoma is a highly malignant tumor. In the past, treatment options like chemotherapy were of limited benefit, and its prognosis, particularly in the advanced stage, was poor. The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape for melanoma and significantly improved patient survival. However, the efficacy of ICIs monotherapy remains limited, with only a small proportion of cancer patients benefiting. It has been proposed that oncolytic viruses (OVs) can significantly increase the density of CD8 + T-cells in tumors by modulating the tumor microenvironment from “cold” to “hot”, and this change can synergistically activate anti-tumor immunity in conjunction with ICIs, thus improving the response rate of ICIs therapy. This change can synergize with ICIs to activate the body’s anti-tumor immunity, thus improving the response rate of ICIs. However, there are still some unanswered questions, such as whether the combination will increase the incidence of adverse reactions. This review systematically combed the available clinical trial data to assess the feasibility and clinical application value of combining ICIs with OVs in the treatment of melanoma, as well as summarized the occurrence of adverse reactions in the clinical studies, analyzed their characteristics, and made management recommendations. Our review constructs a new theoretical framework for melanoma treatment, focusing on directions such as efficacy and adverse effects to provide practical guidance for clinical practice.</p>