Wet-chemical reactions, covering almost all solution-based synthesis in either the oil-phase or water-phase microenvironment, lead to the as-formed products with distinct morphologies, structures, and functionalities. However, crystal nucleation and growth dynamics under those microenvironments for the same material system have not been clarified. Using in situ transmission electron microscopy on the classical II-VI CdSe-based heterostructures with atomic scale resolution, notably, we revealed the formation of Au on the CdSe surface in the oil phase while the AuSe product was nucleated in the water phase. The nucleation was analogous to the two-step amorphous-to-crystalline transition, followed by growth or coalescence into polycrystalline nanoparticles. During the ex situ growth, the majority of AuSe was polycrystalline (∼79%) in the water phase, in contrast to ∼52% in the oil phase. Surprisingly, the proportion of single crystals prevailed, which was significantly increased to ∼76% in the in situ case. Such distinct behaviors were further verified through the liquid-cell environment and elemental characterizations.