Primary spinal cord melanoma (PSCM) and primary pleural melanoma (PPM) are extremely rare entities with scarce cases reported in the literature. We present a case of a 54-year-old male diagnosed with possible primary pleural melanoma and primary spinal melanoma, managed with partial surgical resection, postoperative radiotherapy, and chemotherapy consisting of Ipilimumab, nivolumab, and temozolomide. This leads to decreased symptoms and improved quality of life of the patient. In this case report, we review the literature on PSCM and PPM in detail, addressing the pertinent clinical aspects as well as current and upcoming therapeutic options.