This study deals with the creep-fatigue strength evaluation of a tube-sheet structure made of Mod. Grade 91 steel. Such a structure is one of the components of Japan Sodium Fast Reactor (JSFR) that suffers the most severe loadings in the reactor and one of the most difficult components to design because of its complex three-dimensional semispherical shape with an arrangement of numerous holes. A test model of this component was developed by Japan Atomic Energy Agency and test was subjected to 1873 cycles of severe thermal transient loading in which elevated temperature at 600 °C and 250 °C was flowed using sodium flow repeatedly and kept at the final temperature for 2 h and 1 h, respectively. In this study, 3D finite element model of the component is developed, and heat transfer and stress analysis of this structure were performed using the temperature-dependent Mod. Grade 91 material properties for 100 cycles. Creep-fatigue life of the component is initially evaluated using the stress redistribution locus and simple elastic follow up methods. The creep-fatigue results based on these elastic analyses are compared with the inelastic analysis based procedures that include nonlinear constitutive models e.g., bilinear and Chaboche model coupled with time hardening creep. The creep and fatigue damages using these methods are plotted in the Campbell diagram and predicted life cycles are compared to show the applicability of these methods for life prediction.