Two-dimensional (2D) materials are solid crystals consisting of layered planes of atoms that results in anisotropic properties with strong contrast in in-plane and cross-plane physics. Under very high strain or pressure, the van der Waals gap reduces and the anisotropic differences diminishes leading to interesting physics including phase transition, electronic transition, structure transition, and thermal transitions. All in all, the behaviour of electrons, phonons and photons obey different symmetric rules under vertical pressure. In this talk, we will discuss our research on high-pressure effects on monolayer and multilayer TMDs, black phosphorus and heterostructures and the subsequent dramatic consequences. We find the underlying physics is distinct when comparing monolayer to multilayer counterparts. In addition, performance can be tuned far beyond what is observed in conventional bulk solids. These performance parameters include bandgap, mobility, carrier concentration, etc. Layered nanomaterials represent a new frontier where strain can play an effective role as a degree of freedom in controlling and tuning material structure and properties.