Is it true that a nuclear technology approach to generate electric energy offers a clean, safe, reliable and affordable, i.e., sustainable option? In principle yes, however a technology impact on the environment strongly depends on the actual implementation bearing residual risks due to technical failures, human factors, or natural catastrophes. A full response is thus difficult and can be given first when the wicked multi-disciplinary issues get well formulated and “resolved”. These problems are lying at the interface between: the necessary R&D effort, the industrial deployment and the technology impact in view of the environmental sustainability including the management of produced hazardous waste. As such, this problem is clearly of multi-dimensional nature. This enormous complexity indicates that just a description of the problem might cause a dilemma. The paper proposes a novel holistic approach applying Multi-Criteria Decision Analysis to assess the potential of nuclear energy systems with respect to a sustainable performance. It shows how to establish a multi-level criteria structure tree and examines the trading-off techniques for scoring and ranking of options. The presented framework allows multi-criteria and multi-group treatment. The methodology can be applied to support any pre-decisional process launched in a country to find the best nuclear and/or non-nuclear option according to national preferences and priorities. The approach addresses major aspects of the environmental footprint of nuclear energy systems. As a case study, advanced nuclear fuel cycles are analyzed, which were previously investigated by the Nuclear Energy Agency (NEA/OECD) expert group WASTEMAN. Sustainability facets of waste management, resource utilization and economics are in focus.