The overall goal of this project is to develop novel testing and experimentally validated prediction methodologies for creep-dominated creep-fatigue response of structural materials for advanced reactor systems. The investigations will focus on the characterization and testing of Alloy 617, but the proposed testing and life-prediction methodologies are applicable to other structural materials as well. The research objectives of this proposal are: (1) Perform multi-resolution in-situ and ex-situ testing and imaging analysis for the fundamental creep-fatigue damage mechanism investigation; (2) Develop a new procedure for creep-fatigue testing at the coupon level and generate a database for model validation; (3) Formulate and implement models for simulation of creep-fatigue damage mechanisms and their interactions at the microstructure scale; and (4) Conduct microstructure simulations for creep-fatigue mechanism understanding and develop a microstructure-informed and experimentally validated phenomenological creep-fatigue life prediction model.