Integrated thermal protection system (ITPS) is regarded as one of the most promising thermal protection concepts with both thermal insulation and load-bearing capacities. However, the traditional layout of webs could inevitably lead to thermal short effects and high risk of buckling failure of the ITPS. A topological optimization method for the unit cell of the ITPS was established to minimize the equivalent thermal conductivity and elastic strain energy with the constraint of maintaining structural efficiency. The ITPS was re-designed consulting the optimized cell configuration. In order to control the buckling-mode shape and the associated buckling load of the ITPS, the new design was further optimized, subjected to the total weight of the initial design. Detailed finite element models were established to validate the structural responses. By contrast, the optimized design presents lower bottom surface temperature and better thermal buckling characteristics, performing a better balance between thermal insulation and load-bearing constraints.