Uncertainty analysis is a key element in nuclear power plant deterministic safety analysis using best-estimate thermal-hydraulic codes and best-estimate-plus-uncertainty methodologies. If forward uncertainty propagation methods have now become mature for industrial applications, the input uncertainty quantification (IUQ) on the physical models still requires further investigations. The Organisation for Economic Co-operation and Development/Nuclear Energy Agency PREMIUM project attempted to benchmark the available IUQ methods, but observed a strong user effect due to the lack of best practices guidance. The SAPIUM project has been proposed toward the construction of a clear and shared systematic approach for IUQ. The main outcome of the project is a first “good-practices” document that can be exploited for safety study in order to reach consensus among experts on recommended practices as well as to identify remaining open issues for further developments. This paper describes the systematic approach that consists of five elements in a step-by-step approach to perform a meaningful model IUQ and validation as well as some good-practice guideline recommendations for each step.