The goal of this study was to provide a discrete-continuous scheduling model for optimal operation of the fuel cycle of ITER. The model is designed to minimize the tritium working inventory in the Isotope Separation System (ISS) of the fuel cycle by adopting a two-stage scheduling approach. To consider the effect of pump regeneration schedule on tritium fluctuation in the ISS, the suggested solving algorithm is presented as a two-stage scheduling models: Stage I obtains the optimal pump-regeneration schedule, and Stage II suggests the optimal fuel-transition timing from the ISS to the Storage and Delivery System to minimize tritium working inventory in the ISS. The scheduling model uses discrete-time representation in Stage I and continuous-time representation in Stage II.