Emerging interest in the application of nanomaterials in drug delivery, nanoelectronics, development of sensors, etc. in recent years has led to the search for efficient protocols for tailoring nanomaterial properties and function on a molecular level. In particular, we aim to develop methodologies for modifying material surfaces cleanly and quantitatively using easy-to-implement chemical reactions. To this end, bioorthogonal chemistry — characterized by fast, clean, and biocompatible reactivity — represents an effective tool for the surface engineering of nanomaterial platforms with greater practicality and utility. We seek to incorporate these reactive systems (and their photo-activated analogs to provide spatial and temporal control) onto nanomaterial interfaces and investigate their interfacial chemistry. The integration of interfacial strain-promoted alkyne-azide and alkyne-nitrone cycloadditions (i-SPAAC and i-SPANC, respectively) and interfacial Staudinger-Bertozzi ligation (i-SBL) on material interfaces — namely, gold nanoparticles (AuNPs) — will be discussed with respect to their syntheses, characterization, and execution of their interfacial chemical function to attach, release, and replace molecules on the nanoparticle surface. Our ability to quantitate surface functionalities and monitor the interfacial chemistry on materials will be highlighted. These bioorthogonally reactive materials represent a new class of highly versatile nanoparticle platforms that can be easily derivatized for applications in materials science, chemical biology, and has great potential in the emerging area of self-sorting materials.