Both of the southern and eastern margins of the Tibetan Plateau are bounded by the cratonic blocks (Indian plate and Sichuan basin). However, there are many differences in tectonic deformation, lithospheric structure and surface heat flow between these two margins. What dynamics cause these differences? With the constraints of the lithospheric structure and surface heat flow across the southern and eastern margins of Tibetan Plateau, we constructed 2-D thermal-mechanical finite-element models to investigate the dynamics across these two margins. The results show that the delamination of mantle lithosphere beneath the Lhasa terrane in Oligocene and the rheological contrast between the Indian and Tibetan crust are the two main factors that control the subduction of the Indian plate. The dynamics across the eastern margin of the Tibetan Plateau are different from the southern margin. During the lateral expansion of the Tibetan Plateau, pure shear thickening is the main deformation characteristic for the Songpan–Ganzi lithosphere. This thickening results in the reduction of geothermal gradient and surface heat flow. From this study, it can be seen that the delamination of the mantle lithosphere and the rheological contrast between the Tibetan Plateau and its bounding blocks are the two main factors that control the lithospheric deformation and surface heat flow.