Exploring aqueous nano-fabrication with monodisperse and hierarchical characteristics is fundamentally and technically significant. Herein, we discover that inter-particle nano–nano scale interactions profoundly affect the products’ morphology ranging from polydisperse → monodisperse to individual → hierarchical manipulation. Accordingly, we present a “nucleation-growth-dispersion triple modulation” strategy for fabricating monodisperse Cu_2−xE (E = S, Se, Te) nanocrystals (NCs) and supraparticles (SPs). Such full-process and cross-scale control is conducted by two rationally selected ligands (cysteine and citrate molecules), which are responsible for atom/molecule–nano and nano–nano interaction modulations, respectively. Cysteine reacts with the cations and forms low reactive (cysteine-Cu⁺)_n coordination polymers, which overcomes the commonly concerned nucleation and particle growth induced polydispersity. Citrate, by virtue of its strong negative charge modulated NC–NC interactions, decides the products morphology from polydisperse products to monodisperse NCs to monodisperse hierarchical SPs. These findings not only present new insights into aqueous nano-synthesis chemistry but provide an eco-friendly system for versatile and high-quality nano-entity fabrication.