High-strength aluminum plate alloys are widely used in the aerospace and defense industry due to their high specific strength and good workability. In comparison to the trial-and-error strategies, the design of these alloys can be significantly accelerated by using computational alloy design approaches. In the present study, ICME tools based on the CALPHAD approach are employed for the design of a 7xxx ultra high-strength aluminum plate alloy. The manufacturing process of the designed aluminum alloy should be compatible with conventional casting and wrought processing to a 10 cm thickness plate. Employing a hierarchical system approach for the material design, the relationship between processing-structure-properties is first determined for the high-strength aluminum alloy, and then the key design trade-offs of the property objectives are identified. Aiming in maximizing the yield strength and improving the stress corrosion cracking resistance, elongation, toughness, and quench sensitivity of this alloy, specific alloy and process design criteria are applied. An Orowan precipitation strengthening model is developed to describe the hardening behavior upon aging, while the distribution of grain refining phases is predicted via thermodynamic and kinetic calculations. To increase the resistance to intergranular fracture, the chemical embrittlement potency of the segregating solute is employed as a controlling parameter aiming to achieve grain boundary cohesion enhancement according to the Rice-Wang model. A multi-objective optimization problem is formulated and then the optimum composition and processing parameters are determined for the integrated sub-systems via genetic programming. The present design methodology constitutes a fundamental thermodynamic computational approach that can be used for the design of many materials.