A unique benefit of using the closed-cycle gas turbine and gas turbomachines employed in the Gen-IV nuclear power plant is the flexibility it offers in terms of working fluid usage. This is so because of the self-containing nature of the closed-cycle gas turbine. To this end, the selection of the working fluid for the cycle operation is driven by several factors such as the cycle performance, system design, and component material compatibility with fluid properties, availability, and many more. This paper provides an understanding of the design and operational challenges of switching working fluids for a nuclear powered closed-cycle gas turbine. Using the plant output power of a simple closed-cycle configuration as a baseline condition, two case studies have been presented in this paper to explore the design and operational challenges of switching working fluids. In the first case study, the fluid was switched from nitrogen to air and in the second case study, helium and argon were utilised. In both cases, using thermodynamic flow relationship, the closed-cycle gas turbine turbomachinery components maps were analysed to understand the operational requirements for switching the working fluids. The paper also provided an insight into the turbomachinery component design considerations for this to be achieved. The overarching results from a thermodynamic perspective showed fluids with similar thermodynamic behaviour could be switched during idle synchronous speed.