The advent of nanotechnology has vastly advanced our fundamental understandings on nanomaterials, in particular their surface properties. It has also revolutionized the way we functionalize these materials to exploit novel properties and applications. For example, metallic nanoclusters can be processed into different morphologies on support surfaces and subsequently allow desired reaction pathways to occur. In addition, a great number of metal oxides have been grown into single crystal surfaces with precisely controlled atomic arrangements. They have aided researchers to unlock principles governing the extraordinary chemical and electronic properties of oxides. Furthermore, various functionalities can be introduced to polymers and have resulted in multifunctional nanoparticles with superb surface properties. These nanoparticles can therefore overcome biological barriers and effectively deliver therapeutic agents to the disease sites. Using examples from my research in surface functionalization of metals, oxides, and polymeric nanoparticles, I would like to show how the surface functionalization of diverse materials can be guided by a common principle of understanding material structure-property relationship. The continuing effort in studying surface functionalization of nanomaterials will lead them to a brighter future in the fields of biomedicine, energy, and environment.