An integration environment has been developed for conducting multidiscipline design optimization analysis under uncertainty. It facilitates solution of multiple optimization problems in parallel with multiple sets of objectives and constraints originating from different design disciplines while simultaneously accounting for uncertainty during the optimization process.A seamless general purpose integration capability facilitates exchanging data between the optimization processes and the solvers which are used for evaluating the objective functions and the constraints. Metamodels can be developed and used instead of the actual solvers during the highly iterative optimization process in order to expedite the computations. Uncertainties are introduced in the optimization by considering the constraints which depend on any random variables and any random parameters as probabilistic. Satisfying the probabilistic constraints in the presence of uncertainty introduces sufficient conservatism in the solution and eliminates the need for further application of safety factors. The work presented in this paper considers trajectory, aerothermal, aerodynamic, thermal, and structural computations when performing the design optimization for the Thermal Protection System (TPS) and for the structure of a TSTO upper stage vehicle. Sixteen different sections are considered on the vehicle when designing the TPS. The trajectory bank angle schedule, the angle of attack schedule, the thickness of the sixteen different TPS sections, and twenty seven thicknesses associated with the structure are considered when reducing the overall weight of the vehicle while satisfying the imposed constraints. Uncertainties are considered in three control angles of the trajectory, in the material strength, the thrust load and the 2.5G loads. The results from the multi-discipline optimization without and with uncertainty are discussed, and a comparison between the deterministic and the probabilistic optimum is made.