Skin diseases, including skin cancer, are among the most common and debilitating health problems in the world. One of the novel strategies in the treatment of these diseases is the use of targeted drug delivery nanosystems that can precisely deliver drugs to specific skin layers and increase the effectiveness of treatment. In the meantime, theoretical calculations based on density functional theory (DFT) play a key role in the design and optimization of drug-carrying nanostructures, as they allow the investigation of molecular behaviors, electronic interactions, binding energies, and thermodynamic stability at the atomic scale. In this study, recent computational findings on the interaction of drugs with nanocarriers such as boron nitride nanotubes (BNNT), carbon nanotubes (CNT), fullerenes, and calixarene-based host–guest complexes are reviewed. The results show that BNNT nanotubes have higher binding stability with ALA than CNT and retain better drug properties. Also, functionalization of CNTs with functional groups such as –OH and –COOH improves solubility, biocompatibility, and better control of drug release. Calixarene compounds have also shown high potential in the delivery and recognition of 5-FU. On the other hand, fullerene-derived compounds and the recombinant drug DIT-SAL with favorable electronic and structural properties are considered promising options for the treatment of chronic skin diseases such as cancer and psoriasis. These findings emphasize the importance of the combined use of quantum computing and experimental studies in the development of advanced dermal drug delivery systems with high efficacy and fewer side effects. Furthermore, emerging AI-assisted computational frameworks provide a promising direction to complement DFT-based modeling, enabling faster, large-scale screening of nanocarriers for skin disease treatments.