In recent years, there have been a plethora of nanoengineering approaches for the development of poly(lactide-co-glycolide) (PLGA) nanoparticulate carrier systems. However, overlooking the multifaceted issues in the preparation and characterization of PLGA-based nanoparticles, many reports have been focused on their in vivo behaviors. It is imperative to fully assess technological aspects of a nanoencapsulation method of choice and to carefully evaluate the nanoparticle quality. The selection of a nanoencapsulation technique should consider drug property, nanoparticle quality, scale-up feasibility, manufacturing costs, personnel safety, environmental impact, waste disposal, and the like. Made in this review are the fundamentals of classical emulsion-templated nanoencapsulation methods used to prepare PLGA nanoparticles. More specifically, this review provides insight into emulsion solvent evaporation/extraction, salting-out, nanoprecipitation, membrane emulsification, microfluidic technology, and flow focusing. Innovative nanoencapsulation techniques are being developed to address many challenges existing in the production of PLGA-based nanoparticles. In addition, there are various out-of-the-box approaches for the development of novel PLGA hybrid systems that could deliver multiple drugs. Latest trends in these areas are also dealt with in this review. Relevant information might be helpful to those who prepare and develop PLGA-based nanoparticles that meet their specific demands.