A multi-institutional, multidisciplinary project addresses optimal integration of computational design and efficient experimentation for the accelerated design and development of high performance materials using the example of Nb-based superalloys combining oxidation resistance, creep strength and ductility for aeroturbine applications operating at 1300°C and above. Integrated within a systems engineering framework, the effort tests the limits of ab-initio quantum mechanical methods to accelerate assessment of thermodynamic and kinetic databases enabling comprehensive predictive design of multicomponent multiphase microstructures as dynamic systems. Based on established principles underlying Ni base superalloys, the central microstrucrural concept is a dispersion strengthened system in which coherent cubic aluminide phases provide both creep strengthening and a source of Al for Al2O3 passivation enabled by a Nb-based BCC alloy matrix with required transport and oxygen solubility behaviors. A combination of FLAPW all-electron and VASP pseudopotential calculations assess thermodynamic and molar volume behaviors of L21 Pd2HfAl and B2 PdAl based intermetallics as well as BCC Nb-based solutions. Toward an optimal balance of phase stability and interphase misfit, the L21 phase assessment has been extended to the (Pd,Pt)2(Hf,Zr,Nb)Al system with validation by diffusion couple experiments. To identify slow diffusing species to enhance dispersion coarsening resistance, quantum methods predict an activation energy for Re diffusion in Nb 50% higher than that for Mo in Nb. Employing the DICTRA system, a multicomponent diffusivity database is developed for substitutional alloying elements and interstitial oxygen to enhance the diffusivity ratio of Al to O for promotion of Al2O3 passivation. To minimize O solubility, quantum bond topology calculations show trends in interstitial site charge density supporting a dependence of O chemical potential on solution e/a ratio. Integrating the databases and models thusfar developed, a team of students in an undergraduate Materials Design class has performed theoretical designs of 7 component dispersion strengthened alloys with matrix transport and solubility properties supporting feasibility of Al2O3 passivation at 1300°C.