Metallic nanoparticulates (MNPs) are metal particulate of nanodimensions (such as gold NPs, silver NPs, and iron oxide NPs) that have been attracting the scientist over a century in various fields and now widely exploited for drug delivery and diagnostic applications. These nanostructured materials can be synthesized, and their surface modified/functionalized with different functional groups allow them to conjugate with moieties like therapeutics, diagnostics, and ligands. The various physicochemical properties, advantages, disadvantages, as well as characteristics of the metal nanoparticles, are comprehensively discussed, and insight into the site-specific drug targeting strategies for the management of chronic disorders. This chapter provides the detailed information on the synthesis of MNPs by various methods and characterization, with main emphasis on gene and drug delivery perspectives along with toxicity apprehensions. Present chapter also deals with the interactions of tailored MNPs and biological cells, factors affecting the cellular uptake and the intracellular destiny of MNPs, and also degradation of MNPs and its impact on nanotoxicity based on various literatures.