In order to decrease the nuclear innovation cycle time, the future of nuclear technology is dependent on the acquisition of reliable, real-time in-pile data. Specifically, the development of high temperature irradiation resistant thermocouples (HTIR-TCs) for continuous, accurate, and stable temperature monitoring in reactors exceeding 1250 °C is paramount for process/experiment monitoring, simulation validation, and code development. Prior to deployment, HTIR-TCs are thermally conditioned at temperatures above the maximum service temperature to reduce drift with time at exposure. In this work, effects of thermal stabilization treatments on the properties of thermocouples is predicted and characterized. Modeling and simulation (density functional theory-based) were coupled with experiment to optimize such treatments and predict their behavior at temperature over time. HTIR-TCs were examined before and after the stabilization heat treatment, as well as extended (1000 hour) exposures, for mechanical properties, Seebeck, and chemical behavior.