Metastatic melanoma is a fatal form of skin cancer that has a tendency to 
proliferate more rapidly than any other solid tumor. Since 2010, treatment 
options for metastatic melanoma have been developed including chemotherapies, 
checkpoint inhibition immunotherapies, e.g., anti‑cytotoxic T‑lymphocyte 
antigen‑4 (CTLA‑4) and anti‑programmed death‑1 (PD‑1), and molecular-targeted 
therapies, e.g., BRAF and MEK inhibitors. These treatments have shown not only 
high response rates yet also side‑effects and limitations. Notwithstanding its 
limitations, stem cell therapy has emerged as a new auspicious therapy for 
various tumor types. Since stem cells possess the ability to serve as a novel 
vehicle for delivering therapeutic or suicide genes to primary or metastatic 
cancer sites, these cells can function as part of gene‑directed enzyme prodrug 
therapy (GDEPT). This review focuses on introducing engineered neural stem 
cells (NSCs), which have tumor‑tropic behavior that allows NSCs to selectively 
approach primary and invasive tumor foci, as a potential gene therapy for 
melanoma. Therapy using engineered NSCs with cytotoxic agents resulted in 
markedly reduced tumor volumes and significantly prolonged survival rates in 
preclinical models of various tumor types. This review elucidates current 
treatment options for metastatic melanoma and introduces a promising NSC 
therapy.