Limiting global temperature rise to well below 2 °C according to the Paris climate accord will require accelerated development, scale-up, and commercialization of innovative and environmentally friendly reactor concepts. Simulation-based design can play a central role in achieving this goal by decreasing the number of costly and time-consuming experimental scale-up steps. To illustrate this approach, a multiscale computational fluid dynamics (CFD) approach was utilized in this study to simulate a novel internally circulating fluidized bed reactor (ICR) for power production with integrated CO2 capture on an industrial scale. These simulations were made computationally feasible by using closures in a filtered two-fluid model (fTFM) to model the effects of important subgrid multiphase structures. The CFD simulations provided valuable insight regarding ICR behavior, predicting that CO2 capture efficiencies and purities above 95% can be achieved, and proposing a reasonable reactor size. The results from the reactor simulations were then used as input for an economic evaluation of an ICR-based natural gas combined cycle power plant. The economic performance results showed that the ICR plant can achieve a CO2 avoidance cost as low as $58/ton. Future work will investigate additional firing after the ICR to reach the high inlet temperatures of modern gas turbines.