We first formalize the problem and identify the market factors affecting the nuclear fuel cycle such as the capacity factor, the technical lifetime and the license transient budget, the operational cost and the frequency of safety measures due to excessive cycling. A cost calculation methodology is developed based on physics, economics and regulation with the aim of assisting policy makers and industry. The contribution to the literature is the integration of the nuclear load-following operating mode into the overall nuclear cost calculation, with a deep understanding of the operation of a nuclear flexible reactor and its upstream material flow inventory. First, a physical tool (CLASS, Core Library for Advanced Scenario Simulation) describes the dynamics of a complete fuel cycle of a representative PWR kind reactor and gives insights into the material flow under the constraint of the capacity factor, i.e. the share of the fuel burned to match the nuclear power market demand. ln general, the lower the nuclear power output, the lower the share of the uranium burned, the longer the cycle and the lower the fuel cost. Secondly, a technical-economic model (POLES, Prospective Outlook on Longterm Energy Systems) integrates the cost of the uranium cycle calculated with physics criteria and simulates the French power system in 2030 and 2050 under carbon emissions constraint. Thirdly, Poles' outputs, such as renewables installed capacities and flexibility provided by nuclear power plants, are integrated into a sectoral economic model (EcoNUK, Economic dispatching of NUClear reactors). It is assessed on an hourly basis the operation of the nuclear power fleet over the complete fuel cycle. Model results allow assessing the number of cycles performed with nuclear power reactors, the market demand for nuclear power and a new value of the capacity factor, which can be different from timely aggregated models. The hourly loop shows that punctually nuclear reactors are cycling excessively triggering down the load factor, while eventually they can substitute flexible gas-fired units instead of operating base-load improving therefore the capacity factor. Iterations among disciplines ailow finding stable results in terms of uranium cycle cost and reactors' capacity factors, to ultimately compute the nuclear power generation cost, e.g. the LCOE indicator. Preliminary results show that a limited number of iterations is needed due to robust results from the model Poles in terms of nuclear plants' capacity factors. That is, for a large range of the uranium cycle costs, the nuclear power keeps stable its position in the merit order curve that is deregulated market-specific. Two indicators are instead subject to cost cycle variation, namely the system cost to operate the nuclear power plants and the nuclear generation cost.