Modern drug discovery technologies are discovering more and more potent therapeutic agents with narrow therapeutic windows, thus necessitating the improvement of current particulate drug delivery systems. Conventional single-layered polymeric particles have limited control over drug release profiles, including burst release, the inability to provide zero-order, pulsatile, time-delayed release and controlled release of multiple drugs. In an attempt to better control drug release kinetics, the development of multilayered microparticles has been introduced. In this review, we give an overview of the fabrication and characterization techniques of multilayered polymeric microparticles. We also focus on the one-step solvent evaporation technique, and the key process parameters in this technique that affect the formation of microparticle configurations. In addition, the benefits and challenges of multilayered microparticulate system for drug delivery were discussed. This review intends to portray how distinctive structural attributes and degradation behaviors of multilayered microparticles can be exploited to fine-tune drug release profiles and kinetics.