<p>Molten Salt Reactors (MSRs) promise significant advantages over traditional light water reactors, including enhanced safety and improved fuel efficiency. Among MSR designs, those using fueled fluoride salts have the most extensive operational history and are the focus of this study. In these systems, understanding and controlling salt chemistry is essential to reactor safety and performance. Challenges include preventing the release of volatile uranium species, avoiding unintended metallic uranium deposition, and managing fission product speciation as burnup progresses. These issues impact heat exchanger fouling, component corrosion, and potential criticality fluctuations, which define operational limits. Given the complexity of operating MSRs’ chemical and isotopic inventory, accurate simulation is challenging, particularly with limited experimental data. This work introduces a simulation surrogacy methodology to simplify the reactor system by grouping chemically similar species based on available data, balancing computational efficiency with fidelity. The approach integrates SCALE reactor physics framework for modeling fuel salt depletion and fission product generation with the Molten Salt Thermochemical Database-Thermochemical (MSTDB-TC) and Thermochimica for Gibbs energy minimization to predict species behavior. The methodology is demonstrated for a simple MSR design at key points in its lifetime, addressing operational challenges and safety concerns. Key data gaps, including radiological, neutronic, and quantitative limitations, are identified. Although focused on fueled fluoride salts, this methodology is adaptable to other reactor designs, providing a versatile framework for advancing MSR chemistry simulations. While fundamentally exploratory due to current database limitations, this methodology provides a systematic framework for advancing MSR chemistry modeling and identifying critical data needs.</p>