Skin cancer continues to pose a major global health burden, with the incidence of melanoma projected to reach approximately 510,000 cases and non-melanoma to increase 1.5-fold by 2040. Despite significant advances in cancer therapeutics, conventional treatment modalities for skin cancer, including chemotherapy, are associated with several limitations and adverse effects, such as skin rashes and other cutaneous toxicities. In addition, immune checkpoint inhibitor-based immunotherapies, which are widely used in advanced melanoma, are frequently associated with immune-related adverse events, including endocrinopathies. Moreover, targeted therapies have been posited as the gold standard in treatment; however, their clinical application is often limited by treatment-related toxicities, including cutaneous side effects such as photosensitivity, panniculitis, pruritus, and rare but severe systemic adverse reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome. Recent advances in cancer nanomedicine have opened new avenues for addressing the limitations of conventional therapies by enabling targeted delivery, controlled drug release, and improved pharmacokinetics. Among various nanocarrier systems, solid lipid nanoparticles (SLNs) have emerged as a promising platform due to their biocompatibility, ability to encapsulate both hydrophilic and lipophilic drugs, and enhanced potential to overcome drug resistance. They facilitate enhanced drug solubility, increased bioavailability, and reduced systemic toxicity, making them a particularly attractive strategy for improving therapeutic outcomes in skin cancer management. Current research highlights SLNs as a promising and effective drug delivery system in both melanoma and non-melanoma therapy. They offer significant advantages for the delivery of anti-cancer agents with improved therapeutic outcomes and reduced toxicity in patients. Moreover, it can co-deliver multiple anticancer agents, showing synergistic effects and enabling targeted delivery through surface functionalization. However, significant knowledge gaps persist regarding their in vivo behavior, cellular uptake, biodistribution, and interactions within the tumor microenvironment (TME). The current body of literature emphasizes majorly on drug delivery, and explores the immunomodulatory effects of SLNs in the delivery of immune checkpoint inhibitors or gene therapy, which could enhance anti-tumor immunity. However, future research should focus on advanced imaging and omics techniques to uncover these aspects. Moreover, further exploration is warranted to comprehend the mechanisms of SLNs, and personalized strategies are needed to address existing challenges and enhance therapeutic outcomes.
