This paper summarizes the experience gained in the application of multi-criteria decision making and uncertainty treatment methods to a comparative assessment of nuclear energy systems and related nuclear fuel cycles. These judgment measures provide a means for comprehensive evaluation according to different conflicting criteria, such as costs, benefits and risks, which are inevitably associated with the deployment of advanced technologies. Major findings and recommendations elaborated in international and national projects and studies are reviewed and discussed. A careful analysis is performed for multi-criteria comparative assessment of nuclear energy systems and nuclear fuel cycles on the basis of various evaluation and screening results. The purpose of this paper is to discuss the lessons learned, to share the identified solutions, and indicate promising future directions.