For some time Photodynamic Therapy and electrochemotherapy have been used as alternative therapies against skin cancer. The primary aim of this work was to develop, characterize, and evaluate the in vitro cytotoxic activity of new drug delivery systems based on chitosan nanoparticles containing aminolevulinic acid derivatives such as prodrug (5-ALA and its ester derivative 8-ALA). The second goal of this study was to evaluate the synergistic effect of a combination of classical Photodynamic Therapy and electrochemotherapy, which is routinely utilized to modulate and enhance the permeation of photosensitizers, prodrugs, and other active compounds through the skin, improving the efficiency of PDT in the treatment of cutaneous neoplasms.