Low-permeability (unconventional) hydrocarbon reservoirs exhibit a complex nanopore structure and micro (µm) -scale variability in composition which control fluid distribution, displacement and transport processes. Conventional methods for characterizing fluid-rock interaction are however typically performed at a macro (mm) -scale on rock sample surfaces. In this work, innovative methods for the quantification of micro-scale variations in wettability and fluid distribution in a low-permeability oil reservoir was enabled by using an environmental scanning electron microscope. Live imaging of controlled water condensation/evaporation experiments allowed micro-droplet contact angles to be evaluated, while imaging combined with x-ray mapping of cryogenically frozen samples facilitated the evaluation of oil and water micro-droplet contact angles after successive fluid injection. For the first time, live imaging of fluids injected through a micro-injection system has enabled quantification of sessile and dynamic micro-droplet contact angles. Application of these combined methods has revealed dramatic spatial changes in fluid contact angles at the micro-scale, calling into question the applicability of macro-scale observations of fluid-rock interaction.