The unique properties of polymer-hybrid nanosystems enable them to play an important role in different fields such as biomedical applications. Hybrid materials, which are formed by polymer and inorganic- or organic-base systems, have been the focus of many recently published studies whose results have shown outstanding improvements in drug targeting. The development of hybrid polymer materials can avoid the synthesis of new molecules, which is an overall expensive process that can take several years to get to the proper elaboration and approval. Thus, the combination of properties in a single hybrid system can have several advantages over non-hybrid platforms, such as improvements in circulation time, structural disintegration, high stability, premature release, low encapsulation rate and unspecific release kinetics. Thus, the aim of the present review is to outline a rapid and well-oriented scenario concerning the knowledge about polymer-hybrid nanoparticles use in biomedical platforms. Furthermore, the ultimate methodologies adopted in synthesis processes, as well as in applications in vitro/in vivo, are the focus of this review.