Strain is an inevitable phenomenon in two-dimensional (2D) material, regardless of whether the film is suspended or supported. Moreover, strain is known to alter the physical and chemical properties, such as the band gap, charge carrier effective masses, dielectric properties, chemical reactivity, and many more. One example is the metal-2D material junction, where the interaction at the interface between the contact electrode can be significantly altered by strain. Moreover, the response to strain varies depending on the contact material used. In this study, we explored different substrate roughness levels and investigated the interface properties between monolayer MoS2 and metal using X-ray photoelectron spectroscopy, atomic force microscopy, and Raman spectroscopy. Furthermore, to enable the direct measurement of strain response, I successfully developed a nanoindentation system integrated with a scanning tunneling microscopy (STM) sample holder. The system allows for in-situ reversible control of strain and gate electric fields. It utilizes a gearbox and a piezoelectric actuator, providing precise control of indentation depth at the nanometer level. The 2D materials are placed on a flexible polyimide film to ensure mechanical stability, and a Pd clamp is used to improve the transfer of strain from the polyimide to the 2D layers. The small size of the sample holder (~160 mm2 x 5.2 mm) makes it compatible with a broad range of measurement systems, including atomic force microscopy and Raman spectroscopy, in addition to STM. By employing the novel approach described above, the study has successfully observed atomic precision strain responses of 2D materials like graphene and monolayer MoS2. In their relaxed states, strain mostly arises from local curvature caused by the polyimide surface roughness. However, when the materials are under strained conditions with tented structures, lattice parameters become more sensitive to changes in indentor height, leading to additional stretching strain. The indentation system allows for further adjustments to the indentor and sample configuration, which enable the application of uniaxial strain for measuring the Poisson's ratio. As a future perspective, we identify existing challenges related to performing local spectroscopy and research topics on defect in-gap states in monolayer MoS2.