Abstract: Extending precision synthesis from the molecular scale to the nanoscale is crucial for the atomic-level engineering of nanocrystals for their applications in energy, information, and biomedical nanotechnologies. However, precision nanosynthesis has been a significant challenge due to the complexity of nanostructures. A nanocrystal contains ~10s to ~10,000s of atoms in the core, metal-ligand coordination complexes at the interfaces, and organic molecules on the surfaces. Correspondingly, nanocrystal synthesis involves numerous collisions, exchanges, and reorganizations at hierarchical levels with intricate reaction kinetics and a broad energy landscape from ~1 kJ/mol (intermolecular interactions) to ~1000 kJ/mol (covalent bonds). Here, I will demonstrate how to combine precise coordination and cluster chemistry with colloidal reactions to achieve the rational synthesis of atomically defined semiconductor nanoclusters. Specifically, we “precisionalize” a colloidal cation exchange reaction by using precise Cu2Se clusters as anion templates and Cd(II) complexes as cation carriers, which leads to a precise CdSe cluster with near unity yield. X-ray crystallography and in-situ spectroscopy provide atomic insights into the transformation mechanisms, the structural construction rules, and the origins of chirality and polarity in semiconductor nanomaterials. It is expected that precision nanosynthesis will provide a designable approach to access a library of atomically precise semiconductor nanoclusters with tailored cores and surfaces for their various applications.