The introduction of renewable energy technologies such as wind and solar energy in the electricity market cause the increase of load variations and rapid load changes of large Gas Turbine Combined Cycle (GTCC) power plants. This leads to the evolution of extra thermal stresses in critical parts of the plant such as the boiler. The present study is focused on the development of simulation models that are able to calculate the evolution of thermomechanical stresses in critical components of the boiler. Such models can be useful in analyzing and estimating the fatigue lifetime of boiler components and therefore can be helpful in reducing maintenance costs. This study consists of two parts; In the first part a literature review is presented, along with a fatigue assessment methodology according to the EN 12952-3 standard. Then the mathematical model that has been developed is described. In the second part, the proposed methodology is applied in an existing GTCC power plant using online data. The simulation is focused on the high pressure steam drum of the unit and the results show that the component experiences a cycling loading in daily operation. By implementing a fatigue cycle counting technique based on the rainflow algorithm, the amplitude and mean stress of each identified cycle are determined. Finally, using these outcomes the fatigue lifetime of the component can be estimated. Various simulation scenarios are considered in this study. These include start-up / shut down of the plant, load change and daily operation. According to the simulation results the most severe situation is the start-up where the highest stress amplitudes are observed. Nevertheless, the calculated stresses are well below the yield stress of the material, leading to a theoretically infinite fatigue lifetime. The implementation of the simulation models to the other components of the boiler, such as the superheater headers, can give a better insight to the consequences of cycling modern GTCC power plants.