Metastatic melanoma (MM) is one of the most lethal types of cancer. Although novel immunotherapeutics have been developed recently, still, these drugs fail to save the lives of a third of MM patients. Electrochemotherapy (ECT) is a local treatment of cancer based on a combination of electroporesis and low-dose chemotherapy. In this case report, we present the treatment history of a MM patient treated successfully with ECT and immunotherapy combination as a fifth-line treatment. Our patient was a 39 year-old woman who was diagnosed with nodulary melanoma stage II. Due to a local recurrence, she was given interferon-α treatment. After 6 months, her disease relapsed in the axillary lymph nodes, and temozolamide treatment 150 mg/m2 was initiated. After six cycles on temozolamide, she progressed both in the axillary site and in the lungs. Her BRAF mutation analysis revealed V600E positivity. Hence, BRAF inhibitor-vemurafenib 2′4 tablets per day was initiated. Within 3 months, she responded dramatically both in the axillary site and in the lungs. At the ninth month of treatment, she progressed again, at which time ipilimumab 3 mg/kg was started as a fourth line treatment. However, shortly after, she progressed again and developed a solitary brain metastasis. She was operated and had whole brain radiotherapy. At that point, nivolumab, an antiprogrammed cell death ligand-1 blocker, was the only remaining option. She showed a biphenotypical response to nivolumab; a mass on the anterior axilla was progressing while the other lymph nodes had regressed. Owing to the accessibility of the subcutaneous lesion with external electrodes, ECT was performed using IGEA Cliniprator device through a hexagonal electrode on the progressive mass, while on nivolumab treatment. A complete response was achieved, with no evidence of disease at 4 years since her local recurrence. Eradication of symptomatic, refractory lesions using ECT meets an important clinical need. Whenever a disseminated disease presents with cutaneous/subcutaneous lesions, high efficacy of ECT should be deployed to augment tumor immunogenicity and complement systemic immunotherapies.