Pyroprocessing is being developed at Korea Atomic Energy Research Institute (KAERI), and in recent years, all process equipment required for integrated processes have been examined in the PyRoprocess-integrated Inactive DEmonstration (PRIDE) facility. Based on the successful operation of a pilot-scale facility, a conceptual design for this scale-up facility was actualized. Implementing a “demonstration-scale” hot cell facility is challenging as it is intended to supersede PRIDE and satisfy the increased requirements of larger-scale facilities. This study focused on an inerting strategy for a larger-scale (demonstration-scale) hot cell facility to achieve conditions equivalent to those in a pilot-scale gas-tight argon cell facility. The study applies the inerting strategy to a demonstration-scale hot cell facility beyond that of the currently existing pilot-scale hot cell facility and performs computational fluid dynamics (CFD) simulation with various flow rates to determine an appropriate approach for inerting the target facility. To this end, practical constraints on the simulation are introduced based on experiences from the existing pilot-scale facility. The results show that the purging flow rate should be accurately predicted, and a variable flow rate should be applied to achieve hot cell inerting effectively. The required purging time and amount of inerting source are essential factors in the larger-scale hot cell facility. The study results can be helpful in the design of large hot cell facilities operated under inert conditions.