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Radioisotope Thermoelectric Generators (RTGs) have been used to power NASA missions of various types throughout the past five decades. The most recent RTG iteration, used for NASA’s Mars Science Laboratory, is the Multi-Mission RTG (MMRTG), which is currently the only spaceflight-qualified system available. The U.S. planetary science community has expressed a desire for more power system options to be available to accommodate a range of ambitious future mission concepts across the solar system. Recent advancements in thermoelectric (TE) materials technology have raised a potential for significantly increased efficiency in future RTGs, which helped spur a recent in-depth NASA study of options for future systems. A “next-generation” RTG study was conducted to develop new RTG concepts that could meet the needs of planetary science missions through the 2030s and beyond. A Next-Generation RTG would aim to extend the types of potential NASA missions able to be supported, while fulfilling requirements related to technical risk and schedule. In this study, 21 potential thermoelectric couple configurations were analyzed by considering various high-performance, high-temperature TE materials and segmentation techniques that maximize convertor efficiency and power density. System modularity was explored, and found to be a promising means to offer improved flexibility for NASA mission concepts with varying scope and power requirements. This paper presents the results of the study, demonstrating the viability of developing an updated RTG system design, and defining conceptual system approaches for a new, potentially revolutionary RTG.