The common approach for evaluation of stability of multicomponent substitutional solid solutions using thermodynamic, mechanical, and topological parameters of the constituent elements is developed. The high-temperature systems based on refractory elements (W, Ta, Mo, Nb, V, Ti, Zr, Hf, Cr) are investigated using this approach. Optimal compositions for high-entropy alloys are obtained, and influence of various factors in the formation of stable alloys is described. As shown, the most resistant alloys have non-equiatomic element-contents’ ratios. The agreement between element distribution in experimental alloys and predicted stable compositions are obtained for the W— Ta—Mo—Nb and W—Ta—Mo—Nb—V systems.