Stabilizing a nanocrystalline material against grain growth makes it possible to effectively use the Hall-Petch strength of the nanostructure. This stabilization is often achieved by alloying, which has motivated previous efforts to guide alloy selection. In this work, we substitute niobium for tantalum, both group VB transition metals, in a copper-based nanocrystalline alloy, with the niobium providing an equivalent thermal stabilizing effect as reported for copper-tantalum alloys. However, the thermomechanical strength of the copper-niobium alloy is found to be diminished in comparison to copper-tantalum. This elevated-temperature-strength difference is a result of the solute-contaminant reactant phases, which arise from alternate equilibrium oxides formed between the two solute types. In particular, the misfit strain with temperature is found to be a critical variable for the copper-niobium alloy's thermomechanical strength. These findings highlight that solute-impurity reactions are crucial to nanocrystalline alloy design, particularly for elevated temperature structural applications.