<p>Understanding and controlling friction is crucial for advancements in nanoscale systems and microelectromechanical devices. Moiré superlattices formed on graphene-covered metallic substrates present a unique opportunity to modulate frictional behavior. However, the role of graphene/substrate interaction in lubrication within these heterostructures remains inadequately explored. In this study, molecular dynamics simulations combined with theoretical modeling are employed to investigate the impact of graphene-substrate interactions on friction in moiré heterostructures. The results reveal a nonmonotonic dependence of lateral forces on interaction strength, governed by the competition between graphene wrinkling and elastic energy dynamics. In the weak interaction regime, tip/graphene-adhesion-induced graphene wrinkling enhances friction by increasing pinning atoms. In contrast, strong interactions lead to elastic energy accumulation and relaxation, elevating friction during stick–slip motion. Additional factors, such as normal load, tip size, tip geometry, and tip/graphene interaction, significantly influence frictional behavior. An improved Prandtl-Tomlinson model is developed to validate the findings, demonstrating excellent agreement with simulation results. This work elucidates the mechanisms underlying graphene-substrate-interaction-dependent frictional behavior and offers a framework for tuning tribological properties in two-dimensional materials, enabling the design of advanced MEMS and NEMS with controllable lubrication.</p> Graphical abstract <p></p>