Melanoma is a skin cancer that arises from genetically altered or activated epidermal melanocytes. The prognosis of patients who reach the metastatic phase (stage IV) is grim, presenting a 5-years survival rate between 5% and 19%, depending on the site and extent of the metastatic disease. Currently, there is no definitive cure for metastatic melanoma, and existing treatments are hindered by drug resistance and significant side effects. Moreover, advanced treatment options often fail because of transport limitations, poor targeting capacity, and side effects. The traditional drug testing models mainly based on oversimplified 2D or 3D cell cultures failed in supporting the drug development process, because of their lack of similarity with the complex pathophysiology of the metastatic disease.