Currently, the targeted drug delivery system that has a pivotal role in the future of personalized medicines has gained significant attention toward research as well as commercial ventures. Targeted drug delivery systems, which are also made up of nanoscale drug carrier molecules, are designed for improving the communication of cellular as well as molecular components including biodistribution of tumor-targeted drug (chemo) therapeutics. Nanomaterials are usually bunches of atoms, molecules as well as molecular fragments of nanosized particles (1–100 nm). Multifunctional smart nanoparticles/nanomaterials that are engineered as self-assembled biodegradable particles have been exploited toward targeted drug delivery system. The term "smart" has been introduced for those nanomaterials, which can react in a predictable and specific manner to external/internal stimuli. This feature of such carrier systems to undergo controlled discharge of the loaded drugs not only results in thorough mitigation of their side effects but also enhances their treatment, efficiency. This chapter presents insight on the recent advances, together with the advantages, and drawbacks of various nanosized drug delivery systems, including formulation of nano-Amphotericin B drug as a case study for the treatment of visceral leishmaniasis. Furthermore, this chapter also provides a current overview of the tailored conjugation of targeting ligands and controlled drug release. Different nonmaterial-drug conjugates based on nanoemulsion, nanogel, solid-lipid nanoparticle, liposome, micelles, dendrimer, hyperbranched polymer, carbon nanotube, nanoshell etc. are discussed pertaining to absorption, distribution, metabolism, and excretion along with toxicity.