In the method, a set of limits are defined and a reference core design is generated based on the limits, and includes an initial loading pattern of current fresh fuel bundles arranged in a plurality of fuel locations. A unique subset of fresh fuel bundles is selected for evaluation as the reference core design is subjected to an iterative improvement process. The iterative process includes replacing, at each fuel location, at least one of the current fresh fuel bundles with at least one of the selected fresh fuel bundles, and simulating reactor operation on the reference core design to obtain a plurality of outputs. The outputs may be ranked based on the defined set of limits, and the highest ranked output may be selected as an accepted core design for the nuclear reactor.