Transdermal delivery systems offer a promising alternative route for drug administration to overcome various limitations from other routes. However, several challenges in transdermal delivery must be addressed to enhance therapeutic efficacy, including drug permeation via the stratum corneum, the outermost and most rigid skin layer. Lipid-based nanoparticles, such as liposomes, ethosomes, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers, have been designed to improve drug penetration. Their nanoscale size and hydrophobic properties, resembling those of the stratum corneum, enable them to achieve deeper skin permeation. Nevertheless, drug concentration that reaches systemic circulation following transdermal application of lipid nanoparticles is relatively limited. Hence, microneedles can be combined with lipid nanoparticles to enhance skin permeation by forming microchannels in the stratum corneum, thereby improving the penetration of lipid nanoparticles into the deeper skin layers. To date, three types of microneedles have been combined with lipid nanoparticles which are solid, hollow, and dissolving microneedles. The integration between lipid nanoparticles and microneedles has demonstrated significantly higher skin permeation, transdermal bioavailability, and therapeutic efficacy, with sustained release properties, compared to lipid nanoparticles alone via transdermal delivery. Therefore, the synergistic properties of encapsulated lipid nanoparticles with microneedles can be a promising strategy to improve transdermal delivery systems. © 2025 Elsevier B.V.