Transdermal drug delivery offers many advantages over oral delivery, such as avoiding first-pass metabolism, enhancing the bioavailability of poorly soluble drugs, and providing better patient compliance. However, only small lipophilic molecules can be delivered across the stratum corneum, the outermost layer of the skin. Unfortunately, the delivery of larger molecules remains a challenge. Nanostructured lipid carriers (NLCs) are second-generation lipid nanocarriers composed of biocompatible solid lipids, liquid lipids, surfactants, and co-surfactants. NLCs can be loaded with various classes of drugs, provide a controlled drug release profile, enhance drug stability, and be scaled up without needing organic solvents. This review article discusses the features, composition, formulation processes, and characterization of NLCs and their potential use in transdermal drug delivery.