This paper presents an analysis of VHTR systems with no on-site refueling. The objective of the research effort is to evaluate out-ofcore fuel cycle characteristics focusing on potential front-end composition variations and their impact on back-end management options. Recognizing fuel cycle flexibility of HTGRs, a broad range of fresh fuel vectors is taken into consideration including traditional LEU and transmutation fuels containing TRUs from PWR spent fuel. In this analysis, the primary purpose of added TRUs is to achieve prolonged operation on a single fuel loading. Researchers assessed perturbations of the VHTR spent fuel characteristics (back-end management options) because of the VHTR fresh fuel composition deviations from the chosen reference content. A single-batch autonomous operation (no on-site refueling) offers a number of advantages facilitating deployment in energy-demanding developing regions with limited industrial infrastructure while maintaining system safety and security by design. The study is performed for the hexagonal block core concept within the framework of the ongoing U.S. DOE NERI Project on utilization of TRUs as a fuel component for extended-life VHTRs.