The depletion of light crude oil resources necessitates the efficient development of heavy crude oil, characterized by high density and viscosity. In this work, we used molecular dynamics (MD) simulations to investigate the mechanisms by which two oil-soluble viscosity reducers (VRs) reduce the viscosity of heavy crude oil. Our results reveal that direct interaction between VRs and asphaltene (ASP) aggregates is not the sole pathway for viscosity reduction. Instead, targeting resin (RES) emerges as a critical strategy. The first kind of VR (VR1), with its polar acrylamide head, binds effectively to ASP, reducing the exposure of ASP to other heavy oil components and thereby decreasing the friction between ASP and these components. In contrast, the second kind of VR (VR2), with a maleic anhydride head, tends to disperse away from ASP aggregates, reducing viscosity by weakening the intermolecular interactions between RES and lighter components. These findings elucidate distinct mechanisms by which VRs mitigate the viscosity of heavy crude oil and provide insights for the design of more effective oil-soluble VRs for future heavy oil exploitation.