The increasing interest in developing nanodevices for biophysical and biomedical applications results in concerns about thermal management at interfaces between tissues and electronic devices. However, there is neither sufficient knowledge nor suitable tools for the characterization of thermal properties at interfaces between materials of contrasting mechanics, which are essential for design with reliability. Here we use computational simulations to quantify thermal transfer across the cell membrane–graphene interface. We find that the intercalated water displays a layered order below a critical value of ∼1 nm nanoconfinement, mediating the interfacial thermal coupling, and efficiently enhancing the thermal dissipation. We thereafter develop an analytical model to evaluate the critical value for power generation in graphene before significant heat is accumulated to disturb living tissues. These findings may provide a basis for the rational design of wearable and implantable nanodevices in biosensing and thermotherapic treatments where thermal dissipation and transport processes are crucial.