An overall fixed-bed reactor model that combines a one-dimensional plug flow reactor model with a computational fluid dynamics (CFD) model of the shell-side coolant fluid over a series of individual reactor tubes is presented. The model chemistry is the partial oxidation of o-xylene to phthalic anhydride, a well-studied system for reactor performance. The model is used to investigate the effect of variation in cooling temperature on overall reactor performance: temperature profiles at the wall and centerline and o-xylene conversion. Non-isothermal shell-side cooling temperature profiles are calculated using computational fluid dynamics and heat flux profiles along the reactor tube length. This analysis demonstrates that, with faster coolant flow rates, the coupled fixed-bed reactor and CFD model process outputs approach the nominal case. Alternative shell-side baffle configurations are examined. The calculated coolant velocity profiles, though different between evaluated configurations, result in similar overall reactor performance. However, it should be noted that none of the simulations observe isothermal shell-side coolant temperatures, as is commonly assumed in fixed-bed and plug flow reactor models. This coupled model enables opportunity for further reactor optimization on both the shell-side CFD model and the fixed-bed reactor model, as it can be applied to pilot- and commercial-scale reactors for existing or new chemistries. This model provides a more realistic estimation of the reactor performance, when considering isothermal coolant profiles. Specifically, for the fixed-bed reactor model, alternative catalyst packing schedules (i.e., activity profiles) or feed rates can be considered. Additionally, conditions or individual reactor tubes can be identified that are more prone to runaway.