The primary course of melanoma treatment involves surgery in association with chemotherapy. One potential agent is vinorelbine (VNR). While it displays anti-proliferative activity against melanoma cell lines, it presents a low oral bioavailability and intravenous administration often causes irritation, phlebitis and pain at the injection site. The aim of this study was to develop Pluronic® F-127 (PF-127) hydrogels containing VNR for the transdermal route of administration. Hydrogels composed of either 15% (G15), 20% (G20), 23% (G23) or 25% (G25) PF-127 aqueous solutions were loaded with a VNR propylene glycol solution. Their release and permeation profiles for VNR were evaluated in a Franz diffusion cell. In addition, their rheological behavior, visual aspect during storage and the in silico prediction of VNR absorption using GastroPlus® were evaluated. The G20 and G23 formulations showed similar release and permeation profiles with the G20 demonstrating a higher permeation of VNR at 8h (p<0.05) and cumulative permeated drug amount of 495.2 ± 46.7 μg/cm² at 24h. Further, their activity was tested on the melanoma cell lines SK-MEL28 and MV-3 to evaluate cell viability and proliferation. At VNR concentrations of 75 and 100 μg/mL, cell viability of both melanoma cells was lower in the presence of the G20 formulation than G23 after 24h of treatment although the proliferation profiles were similar. When combined with an in silico pharmacokinetic model, the results suggest that the transdermal administration of VNR could be a promising alternative to intravenous administration and that the G20 formulation would be an excellent candidate for the direct application onto melanomas.