Simple SummaryBasal cell carcinoma (BCC) belongs to one of the most common types of skin carcinoma characterized by high morbidity worldwide. Available therapies are mainly based on non-targeted approaches, which encounter a significant risk of systemic toxicity in several organs. In this work, we discuss a novel approach using targeted therapy-based lipid nanoparticles loaded with classical chemotherapeutic drugs, Hedgehog inhibitors, or photosensitizers for improved localized therapy while reducing adverse side effects and systemic toxicity. New therapeutic topical strategies are presented despite the limited number of reports available.Skin cancer is the most common type of carcinoma diagnosed worldwide, with significant morbidity and mortality rates among Caucasians, in particular basal cell carcinoma (BCC). The main risk factors of BCC are well-identified, and there are many chemotherapeutic drugs available for its treatment. The effectiveness of therapeutic options is governed by several factors, including the location of the tumor, its size, and the presence of metastases (although rare for BCC). However, available treatments are based on non-targeted approaches, which encounter a significant risk of systemic toxicity in several organs. Site-specific chemotherapy for BCC has been proposed via the loading of anticancer drugs into nanoparticles. Among various types of nanoparticles, in this review, we focus on potential new regimens for the treatment of BCC using classical anticancer drugs loaded into novel lipid nanoparticles. To meet patient aesthetic expectations and enhance the effectiveness of basal cell carcinoma treatment, new therapeutic topical strategies are discussed, despite a limited number of reports available in the literature.