The experimental Co–Re-based alloys are being developed for high-temperature applications for service temperatures beyond 1100°C. One of the main tasks of this research is to find the optimal chemical composition. Thermodynamic calculations are very helpful for composition selection and optimization. In this study, thermodynamic calculations were used to identify potential alloying elements and to determine suitable concentration ranges to improve properties, such as strength and oxidation resistance that are essential for high-temperature structural materials. The calculated ternary phase diagram of the Co–Re–Cr system was used to design the reference model alloy. Corrosion products formed under different atmospheric conditions were reliably predicted for a number of model Co–Re-based alloys. Pre-oxidation treatment, a common method used to improve the oxidation resistance of alloys in aggressive atmosphere, was successfully designed based on thermodynamic considerations.