Background/Objectives: Skin cancers belong to the most frequent cancer type with over a million cases per year. Presently, transdermal drug delivery systems (TDDS) are an attractive drug delivery route, but they still face some limitations due to the resistance of human skin. Methods: Here, Sonidegib, PEDOT:PSS, and gelatins were employed as the model drug, drug carrier, and drug matrix, respectively. Results: Gelatin hydrogels were fabricated via the physical crosslinking to avoid toxicity towards the human skin. PEDOT:PSS was synthesized by chemical oxidative polymerization as the drug carrier. Sonidegib first interacted with PEDOT:PSS before they were embedded into the gelatin hydrogels. In the release and release-permeation experiments, the amounts of Sonidegib released and permeated were investigated under the effects of gelatin types, concentrations, pH values, PEDOT:PSS, and electrical voltages. For the effect of gelatin types, the BG gelatin provided higher amounts of Sonidegib release than PG from the higher electrorepulsive force. Under applied electrical voltages and with PEDOT:PSS present, the amounts of Sonidegib release and release-permeation amounts increased as PEDOT:PSS assisted in providing higher electroosmosis and electrorepulsive forces. Conclusions: In summary, PEDOT:PSS in the BG hydrogel is demonstrated here as a potential drug carrier to improve the Sonidegib release and release-permeation iontophoretically for TDDS.