Metastatic melanoma is extremely refractory to existing chemotherapeutic drugs and bioimmune adjuvant therapies, and the life span of patients with metastatic melanoma is often measured in months. Understanding the mechanisms responsible for the development of tumor metastasis is critical for finding successful curative measures. An expending amount of data reveal the importance of inflammatory microenvironment and stroma in cancer initiation and progression, which brings new directions and approaches to cancer treatment. This review will summarize current data on the role of the tumor microenvironment in shaping the metastatic phenotype of melanoma.