Quantum dots are promising building blocks for important applications including photovoltaic, light emission, transistors and bioimaging due to their unique size- and shape-dependent optical and electronic properties. The ability to tune optical and electronic properties of quantum dots by engineering their size, shape, and composition has proved to be a versatile way to interrogate structure–property relationships in quantum dots. Here we present a new method to engineer quantum dot assemblies and to probe their structure-property relationships through stress-induced phase transformation and their exchange coupling during high-pressure compression. We show that under hydrostatic pressure, the unit cell dimension of a 3-dimensional (D) ordered quantum dot superlattice can be manipulated to shrink and swell reversibly, allowing fine-tuning of interparticle separation to probe optical coupling in the supertlattice. Further, beyond a threshold pressure, quantum dots are forced to connect with neighboring dots to form new classes of chemically and mechanically stable 1-3D nanostructures including nanorods, nanowires, nanosheets, and nanoporous networks which cannot be achieved by traditional top-down or bottom-up methods. Moreover, through in situ high-pressure synchrotron-based x-ray scatterings and optical absorption measurements, we discovered Hall-Petch-like size-dependent elastic stiffness and size-dependent pressure coefficient of energy gap in quantum dots. Stress-induced phase transformation and exchange coupling provides new insights for fundamental understanding of chemical and physical properties of quantum dots.