Shale reservoirs contain omnipresent nanopores. The fluid transport phenomena on the nanoscale are significantly different from that on the macroscale. The understandings of fluid transport behavior, especially multiphase flow, are still ambiguous on the nanoscale and the traditional hydrodynamic models are insufficient to describe the fluid flow in shale. In this work, we firstly use a molecular dynamics simulation to study the oil–water two-phase flow in shale inorganic quartz nanopores and investigated the unique interfacial phenomena and their influences on fluid transport in a confined nanospace. The results of the molecular simulation revealed that the water-oil-water layered structure was formed in quartz nanopores. There is no-slip boundary condition between water and quartz surface. The density dip and the extremely low apparent viscosity of the oil–water interface region were observed. The liquid–liquid slip effect happened at the oil–water interface. Based on the nano-effects obtained by the molecular simulation, two mathematical models were proposed to describe the nanoscale oil–water two-phase flow, considering both the solid–liquid and liquid–liquid interfacial phenomena, and the performances of two mathematical models were validated. This study shed light on the flow behaviors of oil and water on the nanoscale, and provides the theoretical basis for scale-upgrading, from the nanoscale to the macroscale.