Access to safe and reliable large-scale geologic storage sites for CO2, H2 and natural gas is integral to energy transition. Efficient use of subsurface formations as storage sites requires reliable predictions of flow processes. In addition to the complexity and uncertainty associated with these systems, the severe predictive limitations of macroscale models of flow and transport adversely affect our ability to engineer subsurface systems reliably. This short course offers a statistical mechanics framework that is firmly grounded in the physics of multiphase flow in permeable media and incorporates non-locality considerations associated with the spatiotemporal scales of large-scale systems.