Abstract: China has achieved significant breakthroughs in both the newly installed capacity and power generation of renewable energy, thus urgently necessitating nuclear power plants to participate in grid peak regulation. However, the traditional fuel management models, which adhere to fixed annual or 18-month refueling cycles, lack flexibility and are unable to adapt to the changing power generation demands of modern nuclear power plants. Enhancing the flexible fuel management in nuclear power plants has emerged as a common concern within the industry. In this paper, a flexible fuel management strategy that encompasses both annual and 18-month refueling modes was introduced. Each mode was capable of operating independently for extended periods and could be seamlessly switched between based on the specific needs of the nuclear power plant. In the flexible fuel management strategy, the 18-month refueling mode incorporated a dual-enrichment core loading scheme, consisting of fuel assemblies with enrichment levels of 4.45% and 4.95%, to cater to the plant’s need for extended cycle lengths during periods of ample power generation demand. Conversely, the annual refueling mode employed a dual-enrichment core configuration of 4.0% and 4.45% enrichments, tailored to accommodate shorter cycle lengths in scenarios of insufficient power generation. The characteristic of the transitional cycle between these two modes was a substantial utilization of components with an intermediate enrichment of 4.45%, facilitating a rapid and seamless transition. Based on the designed fuel management schemes, comprehensive research was conducted, encompassing general fuel management practices, key neutronic parameters, and accident safety analysis and evaluation. The results demonstrate that the flexible fuel management scheme effectively spans the range of 309 EFPD to 549 EFPD, efficiently addressing the diverse energy requirements for both annual and 18-month refueling cycles, thereby significantly enhancing fuel management flexibility. Notably, the core design and safety analysis parameters closely align with those observed in the current 18-month refueling practice, ensuring compliance with pertinent safety thresholds. Remarkably, the successful utilization of a unified set of neutronic parameters to encapsulate both fuel management modes streamlines the safety evaluation process during both engineering design and refueling design stages. Furthermore, flexible fuel management exhibits minimal impact on nuclear power plant systems and equipment, rendering it a viable option for engineering implementation. Compared to the reference power plant, this scheme improves fuel management flexibility, reduces fuel loss caused by early shutdown, increases average discharge burnup, and introduces the cost of fuel management improvements required to meet changes in power generation demand. Therefore, the economic benefits are significant.