This review aims to explore the current methods and advancements in nail permeation, with a focus on the potential of ultrashort pulse lasers to enhance drug delivery. The treatment of nail diseases, such as onychomycosis, is particularly challenging due to the dense structure of nails, which hinders drug permeation. We reviewed traditional methods that are used to enhance drug penetration; however, these methods are often limited by discomfort, infection risks, and inadequate drug permeability. Laser therapy offers a novel perspective in enhancing transungual drug delivery by creating channels on the nail surface without damaging the nail root or bed, thus improving drug absorption. However, common lasers (such as CO₂ lasers) may increase the target temperature beyond the thermal denaturation threshold, thus causing thermal damage to the nail bed and underlying tissues. This can also induce cracks and tissue debris, thus potentially spreading fungal pathogens in cases of onychomycosis. We specifically noted the potential of ultrashort pulsed lasers, which operate in the femtosecond range, to produce high peak power with minimal thermal damage to surrounding tissues. These lasers can create micropores on the nail plate via cold ablation, thus making them promising tools for improving the treatment of nail diseases. However, experimental data on this method are limited, and further studies, including histological research, are needed to validate its effectiveness in enhancing local drug permeability. This represents both a challenge and an opportunity for advancing nail disease treatments.