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It is well established that Re and Ru additions to Ni-base superalloys result in improved creep performance and phase stability. However, the role of Re and Ru and their synergetic effects are not well understood, and the first step in understanding these effects is to design alloys with controlled microstructural parameters. A computational approach was undertaken in the present work for designing model alloys with varying levels of Re and Ru. Thermodynamic and first principles calculations were employed complimentarily to design a set of alloys with varying Re and Ru levels, but which were constrained by constant microstructural parameters, i.e., phase fractions and lattice misfit across the alloys. Three ternary/quaternary alloys of type Ni-Al-xRe-yRu were thus designed. These compositions were subsequently cast, homogenized and aged. Experimental results suggest that while the measured volume fraction matches the predicted value in the Ru containing alloy, volume fraction is significantly higher than the designed value in the Re containing alloys. This is possibly due to errors in the thermodynamic database used to predict phase fraction and composition. These errors are also reflected in the mismatch between predicted and measured values of misfit.