The current waste management strategy for spent nuclear fuel (SNF) mandated by the US Congress is the disposal of high-level waste (HLW) in a geological repository at Yucca Mountain. Ongoing efforts on closed-fuel cycle options and difficulties in opening and safeguarding such a repository have led to investigations of alternative waste management strategies. One potential strategy for the US fuel cycle would be to make use of fuel loadings containing high concentrations of transuranic (TRU) nuclides in the next-generation reactors. The use of such fuels would not only increase fuel supply but could also potentially facilitate prolonged operation modes (via fertile additives) on a single fuel loading. The idea is to approach autonomous operation on a single fuel loading that would allow marketing power units as nuclear batteries for worldwide deployment. Studies have already shown that high-temperature gas-cooled reactors (HTGRs) and their Generation IV (GEN IV) extensions, very-high-temperature reactors (VHTRs), have encouraging performance characteristics. This paper is focused on possible physics features of TRU-fueled VHTRs. One of the objectives of a 3-year U.S. DOE NERI project was to show that TRU-fueled VHTRs have the possibility of prolonged operation on a single fuel loading. A 3D temperature distribution was developed based on conceivable operation conditions of the 600MWth VHTR design. Results of extensive criticality and depletion calculations with varying fuel loadings showed that VHTRs are capable for autonomous operation and HLW waste reduction when loaded with TRU fuel.