Nanoparticles play a central role in the rapidly growing nanoscience and nanotechnology fields. Atomic level tailoring of nanoparticles is of great importance in order to map out the structure-property relationships. Recent success in the synthesis of atomically well-defined nanoparticles has offered exciting opportunities to pursue many fundamental issues that were difficult to tackle with polydisperse nanoparticles. This talk will present several cases of single-atom, single-electron level manipulations of metal nanoparticles, such as doping a single Ag or Cu atom into a gold nanoparticle and site-specific “surgery” of surface motifs of a nanoparticle with controlled charge state. Such atomic-level manipulations provide unique opportunities for investigating how the structure and composition precisely impact the particle’s properties and functionality at the single-atom, single-electron level. New strategies for achieving such goals have been devised. Overall, the pursuit of single-atom level tailoring opens up new opportunities for controlling nanoparticles on an atom-by-atom basis.