The greatest limitation in the development of transdermal drug delivery systems is that only a few drugs can permeate the skin due to the barrier function of the stratum corneum. Active and passive methods are generally available for improving the ability of drug transdermal delivery. However, nanoparticles, as a passive approach, exhibit capacity-constrained permeation enhancement. Thus, microneedle-mediated nanoparticles possess enormous potential and broad prospects. Microneedles promote the penetration of macromolecules by creating microchannels on the skin surface. In this review, the prevailing subknowledge on microneedles (mechanism, classification, and applications of microneedles combined with nanoparticles) is discussed to provide a guideline for readers and a basic reference for further in-depth studies of this novel drug delivery system.