Porosity and permeability are the key factors in assessing the hydrocarbon productivity of unconventional (shale) reservoirs, which are complex in nature due to their heterogeneous mineralogy and poorly connected nano- and micro-pore systems. Experimental efforts to measure these petrophysical properties posse many limitations, because they often take weeks to complete and are difficult to reproduce. Alternatively, numerical simulations can be conducted in digital rock 3D models reconstructed from image datasets acquired via e.g., nanoscale-resolution focused ion beam–scanning electron microscopy (FIB-SEM) nano-tomography. In this study, impact of reservoir confinement (stress) on porosity and permeability of shales was investigated using two digital rock 3D models, which represented nanoporous organic/mineral microstructure of the Marcellus Shale. Five stress scenarios were simulated for different depths (2,000–6,000 feet) within the production interval of a typical oil/gas reservoir within the Marcellus Shale play. Porosity and permeability of the pre- and post-compression digital rock 3D models were calculated and compared. A minimal effect of stress on porosity and permeability was observed in both 3D models. These results have direct implications in determining the oil-/gas-in-place and assessing the production potential of a shale reservoir under various stress conditions.