applications of 2D materials emerging at large strain levels. [8][9][10] Considering difficulties associated with building a microelectromechanical system for straining freestanding 2D materials, [11] 2D materials were often transferred onto a substrate such that the strain can be introduced to the 2D material by controlling the deformation of the bulk substrate. [12] Such fact has led to significant advances in the strategies for straining 2D materials with a film-substrate system, as well as in interface metrologies for the van der Waals (vdW) interaction between the 2D material and its substrate.Here, we first summarize recent experimental achievements on realizing mechanical strain to substrate-supported 2D materials by categorizing the deformation modes of the 2D material-substrate system. These deformation modes include in-plane modes caused by epitaxy, thermal-expansion mismatch, and stretching/compressing the substrate, as well as out-of-plane modes caused by wrinkling and buckling of 2D materials, bulging and poking 2D materials, and transferring 2D materials on a patterned substrate. We then review recent experimental characterizations of the mechanical response of 2D material-substrate interfaces to in-plane shear deformations and out-of-plane delamination. This is not meant to be an all-encompassing analysis of the broad-field topic of strain engineering, but instead, we point out how mechanical deformations are achieved into 2D materials within the film/ substrate system and how the mechanics of interfaces govern these deformation mechanisms. The goal is to deterministically apply both strain magnitude and strain distribution into these atomically thin films and ultimately achieve strain-coupled fundamental physics and chemistry, and exciting applications in a controllable manner. Considering the interdisciplinary nature of research in this field, we also refer the readers to comprehensive reviews from relevant perspectives, including synthesis of emerging 2D materials, characterizations of the strain in 2D materials (especially via the Raman spectroscopy), and applications of mechanically strained 2D materials. [6,13,14] 2D Materials