Nanomaterials (NMs) are ultrafine materials made of different organic and/or inorganic fabrics that have a size range of 10 to 300 nm. Nanomaterials are widely applicable in many fields, such as energy and the environment, health and medicine, and disease detection, treatment, and prevention. At the beginning of their research and exploration, naïve nanomaterials were investigated for their potential applications in all of these fields. However, as time went on and research methodologies, instruments, and techniques advanced, a significant amount of changes and adjustments to their structural, morphological, and physicochemical properties became apparent. Due to this, their capacities and properties such as targetability, drug entrapment efficiency, cellular uptake, preferential accumulation at the desired site and specific interactions with the desired receptors have improved significantly. Additionally, their therapeutic efficacy has improved, leading to a notable increase in the likelihood that they will be useful in clinical settings. The functionalization of nanomaterials in general and nanoparticles in particular to alter their surfaces involves a process that seeks to significantly enhance and add some beneficial qualities for the usage of nanoparticles in biomedical applications. Various kinds of nanomaterials can be employed in the initial stages of functionalization because of their unique chemical characteristics and exposed functional groups. In this chapter, we discussed surface modification, functionalization and bioconjugation of nanomaterials for targeted drug delivery.