Using ultra-high-resolution aberration-corrected S/TEM imaging and spectroscopy, this talk will discuss our recent efforts on the determination of the defect chemistry and sub-Angstrom relaxation effects in nanostructures around at the interfaces in the family of 2D crystal heterostructures. In the family of 2D crystal transition metal dichalcogenides (TMDs) alloys, we report how on anisotropy of the building blocks in the 2D heterostructure, such as ReS2/MoS2 and WS2/Graphene, and their epitaxy and strain at the interface can affect their nucleation and growth. This work will further uncover the structural distortions that occur in these heterostructure across various length scales and reveals the underlying physics of the formation of such heterostructures and their strain state resulting from CVD synthesis.