Using the Thermo-Calc implementation of the CALPHAD approach, high-throughput screening of the Co–Cr–Fe–Mn–Ni system was implemented to find ‘islands’ of single phase FCC structure within the compositional space in order to reduce the cost of this well-studied alloy system. The screening identified a region centred around Co10Cr12Fe43Mn18Ni17, reducing the material cost compared to the equiatomic alloy by ∼40%. The alloy was experimentally investigated at room and elevated temperatures, including in-situ tensile testing. The alloy was found to possess slightly lower strength compared to the equiatomic alloy at room temperature, however, exhibited excellent thermal strength up to 873K. Deformation twinning was observed after tensile testing at room temperature, primarily attributed to the reduced stacking fault energy (SFE), which was proven by a thermodynamic model for calculating the SFE. The softening behaviour at room temperature can be explained through solid solution hardening (SSH), whereby a modified approach to Labusch's model was used to calculate the SSH in reported alloys in this study within the Co–Cr–Fe–Mn–Ni system. The modified models for SFE and SSH are proposed to be implemented into high-throughput screening algorithms for accelerated alloy design towards specific mechanical properties.@en