Mucosal melanomas arise from melanocytes located at various mucosal membranes, which demonstrate a clear demographic and ethnic disparity. This subtype of melanoma has more aggressive course and poorer prognosis than other subsets of melanomas. Due to their rarity, there is no well-established protocol of staging and treatment of mucosal melanomas. Significant advances have been achieved in novel immunotherapeutic and specific targeted agents for metastatic melanomas. For mucosal melanoma patients especially without known gene mutation, anti-angiogenic therapy combined with chemotherapy or other targeted drugs has shown promising efficacy, either as first- or second-line treatment. In some subset analysis, patients with mucosal melanoma, harboring wild type BRAF, might get more clinical and survival benefits than cutaneous ones. Therefore it is rational to further study these therapeutic strategies in the group of mucosal melanoma. Chemotherapy or biochemotherapy only showed limited efficacy without significant survival improvement, but larger sample size study is still required. Herein we presented a comprehensive review of chemotherapy/biochemotherapy and anti-vascular endothelial growth factor (anti-VEGF) therapy in metastatic mucosal melanoma.