Wetting phenomena of oil/water/solid systems are fundamentally governed by the stability of confined water film and interaction mechanism between oil droplet and solid surface in water. Herein, droplet probe AFM was used to quantify the surface forces of model oil droplets including toluene and heptol in presence of interfacial asphaltenes interacting with mica surfaces of varied hydrophobicity in different water environments. It was found that adsorption of asphalenes at oil/water interface could result in the enhanced electrical double layer (EDL) repulsion at low salinity while strengthen the steric repulsion at high salinity, both of which contributed to a more stable water film between oil droplets and mica surfaces, inhibiting oil droplet attachment. Addition of heptane strengthened the repulsive EDL force and steric hindrance since more asphaltenes were adsorbed onto the interface. For hydrophobized mica surface, the attractive hydrophobic interaction could overcome steric hindrance due to interfacially adsorbed asphaltenes, thereby inducing strong attachment and adhesion of oil droplet. Our results demonstrate the nanomechanical mechanism underlying the interactions between oil droplets and solid surfaces in presence of interfacial materials, which can further explain the wetting of oil/water/solid systems in many engineering applications such as oil fouling and corrosion, and oil/water separation.