The treatment of patients with malignant melanoma remains complex and unsatisfactory. Conventional treatment strategies have been approximately ineffective. Dacarbazine (DTIC) is identified as one of the most effective chemotherapy drugs against melanoma with a response rate of around 15–20%. Numerous patients with melanoma who primarily respond to surgery subsequently relapse. Obviously, there is an essential need for better identification, and the improvement of potential treatments is warranted. One such treatment is photodynamic therapy (PDT), in which an agent (photosensitizer, PS) produces reactive oxygen species (ROS) post-irradiation of cancer cells (containing PS). This study reviews the current discovered potential of PDT and their combinations in treating metastatic melanoma and discusses the impact of different PDT strategies on this cancer. Based on different studies, we realize that PDT at different strategies has shown powerful anti-cancer effects on reducing cell viability, metastasis ability, and the induction of apoptosis in different types of melanomas (in vitro and/or in vivo studies). Importantly, promising outcomes have been reported in the reduction of recurrence rate after PDT-treatment. Also, PDT is a manageable therapeutic approach that may offer an additional powerful option for adjuvant therapy of patients with melanoma. Manuscript profile