The Mancos Shale of the San Juan Basin has been an important resource for the exploration and development of oil and gas. However, as with most unconventional plays, the shales have low porosity and extremely low permeability with predominantly nanometer-sized pores. Thus, it is critical to understand the nanopetrophysical properties of the reservoir so a proper assessment of the reservoir quality can be made. Working with three as-received core samples from three different wells of the Tacito Marine Bar and Offshore Mancos play types, we have developed an initial understanding of the nanopetrophysical properties of the pore structure as well as fluid-rock interactions in these tight reservoirs. We have performed a suite of integrated tests, such as mercury intrusion porosimetry (MIP), low-pressure nitrogen physisorption, core plug porosity and permeability, scanning electron microscopy imaging, water immersion porosimetry after vacuum pulling, contact angle, and fluid imbibition. In addition, we obtained supplementary data for total organic carbon, X-ray diffraction, and pyrolysis to further evaluate reservoir quality. The Mancos Shale samples exhibit petrophysical characteristics that are controlled by a predominant presence of nanometer-sized pore space, with 56%–96% pore volumes present as 3.4–50 nm in pore-throat sizes, as shown by the MIP approach. Contact angle and fluid imbibition tests demonstrate that samples are oil wet to mixed wet, with a tendency of pore networks to imbibe oil over water. The findings from integrated pore structure and wettability studies provide a database and some insights, from the perspectives of nanopetrophysical characterization, into the reservoir quality of the Mancos Shale.