By utilizing nanoparticles to upload and interact with several pharmaceuticals in varying methods, the primary obstacles associated with loading two or more medications or cargos with different characteristics may be addressed. Therefore, it is feasible to evaluate the benefits provided by co-delivery systems utilizing nanoparticles by investigating the properties and functions of the commonly used structures, such as multi- or simultaneous-stage controlled release, synergic effect, enhanced targetability, and internalization. However, due to the unique surface or core features of each hybrid design, the eventual drug–carrier interactions, release, and penetration processes may vary. Our review article focused on the drug’s loading, binding interactions, release, physiochemical, and surface functionalization features, as well as the varying internalization and cytotoxicity of each structure that may aid in the selection of an appropriate design. This was achieved by comparing the actions of uniform-surfaced hybrid particles (such as core–shell particles) to those of anisotropic, asymmetrical hybrid particles (such as Janus, multicompartment, or patchy particles). Information is provided on the use of homogeneous or heterogeneous particles with specified characteristics for the simultaneous delivery of various cargos, possibly enhancing the efficacy of treatment techniques for illnesses such as cancer.