Melanoma, both locally progressed and metastatic, has generally had a terrible prognosis. Long-term follow-up of both targeted treatments and immune checkpoint inhibitors had shown their survival advantage in stage IV melanoma, and further trials had demonstrated relapse-free survival benefits from these targeted and immunotherapeutic medicines in the adjuvant context. The use of neoadjuvant chemotherapy for locally progressed melanoma, including in-transit disease, was recently being researched for various studies. Early findings from clinical trials employing either combination targeted treatment or immune checkpoint inhibitors had proved to be promising. Although the neoadjuvant therapy was likely to reduce surgical morbidity, balancing therapeutic efficacy and toxicity had already proven difficult in the use of combination immune checkpoint inhibitors prior to surgery. While there had been an increase in relapse-free survival, greater follow-up of patients undergoing neoadjuvant therapy required reporting on long-term results. 

Additionally, neoadjuvant treatment opened up several new avenues for translational research to identify predictive biomarkers for targeted therapy and immune checkpoint inhibitors. Evidence of early treatment resistance might potentially lead to the development of innovative combination medicines for future clinical trials. While neoadjuvant therapy in locally advanced melanoma showed promising results, further research was needed to identify effective regimens with reasonable toxicity.