Extensive effort is dedicated to developing 2D materials as an alternative to Si‐based semiconductor technology. As the size decreases, heat dissipation at various interfaces becomes increasingly important in controlling device performance. On the other hand, the high interfacial thermal resistances can be applied for thermoelectric devices or thermal insulators by achieving ultralow thermal conductivity via nanostructuring. Here, it is found that a) the thermal and electrical conductance of the Au/MoS2 monolayer interface can be tuned by changing the interfacial chemical properties through N ‐methyl‐2‐pyrrolidone (NMP) wet cleaning while preserving the MoS2 structure; b) the effectiveness of the NMP cleaning process, which removes surface adsorbates, exhibits a temperature dependence; c) experimental results demonstrate that adequate oxygen adsorbates at the Au/MoS2 interface significantly improve the thermal and electrical conductance, in agreement with the simulation results. The interfacial thermal conductance increases by 339.87% when oxygen adsorbates are partially removed and decreases by 74.37% as a sharp interface exists (oxygen adsorbates are removed) compared to the as‐deposited interfaces. The electrical conductance shows up to 2 order increase after NMP cleaning. This finding can both enhance the heat dissipation in functional devices and provide new options for the interface design of thermal insulating thin films.