As a realistic comprehensive optimization method of the TSTO spaceplane, a multi-objective optimization using a multi-objective genetic algorithm (MOGA) and a robust optimization using a design for six sigma (DFSS) have been developed. The multi-objective optimization revealed the strong trade-off relation between the gross take-off weight and the Orbiter separation time minimizations. It also indicated that the propulsion parameter which controls the flow rate of captured air during supersonic flight plays an important role in this trade-off relation. The robust optimization, in consideration of both the objective function optimality and robustness of the gross take-off weight, indicated that the use of larger thrust engine with less fuel leads to the improvement of optimality. On the other hand, the robustest design did not coincide with the optimum solution in terms of the objective function. This result indicated that it is necessary to balance the enlargement of fuel with the enlargement of engine thrust for the improvement of robustness in the robust optimum solutions.