In this study, enhanced oil recovery (EOR) techniques—namely low salinity and nanofluid EOR—are probed at the nanometer-scale using an atomic force microscope (AFM). Mica substrates were used as model clay-rich rocks while AFM tips were coated to present alkyl (-CH3), aromatic (-C6H5) and carboxylic acid (-COOH) functional groups, to simulate oil media. We prepared brine formulations to test brine dilution and cation bridging effects while selected concentrations (0 to 1 wt%) of hydrophilic SiO2 nanoparticles dispersed in 1 wt% NaCl were used as nanofluids. Samples were immersed in fluid cells and chemical force mapping was used to measure the adhesion force between polar/non-polar moieties to substrates. Adhesion work was evaluated based on force-displacement curves and compared with theories. Results from AFM studies indicate that low salinity waters and nanoparticle dispersions promote nanoscale wettability alteration by significantly reducing three-phase adhesion force and the reversible thermodynamic work of adhesion, also known as adhesion energy. The maximum reduction in adhesion energy obtained in experiments was in excellent agreement with existing theories. Electrostatic repulsion and reduced non-electrostatic adhesion are prominent surface forces common to both low salinity and nanofluid EOR. Structural forces are complex in nature and may not always decrease total adhesion force and energy at high nanoparticle concentration. Wettability effects also depend on surface chemical groups and the presence of divalent Mg2+ and Ca2+ cations. This study provides fresh insights and fundamental information about low salinity and nanofluid EOR while demonstrating the application of force-distance spectroscopy in investigating EOR techniques.