The casting process variations of stable solidified cast irons offer the opportunity for significant design flexibility. Thus, the component geometry of parts can be adjusted to local loads, which can be assessed by modern simulation techniques already at early stages of the product development process. Thermo-mechanical loads increase the complexity of the interactions between local loads and the corresponding damage processes significantly. This can be attributed to the nonlinear mechanical deformation behaviour resulting from cyclic elasto-plastic deformation as well as time-dependent creep processes, which have to be taken into account in the mechanical simulation. In addition, the dominating damage mechanisms are strongly affected by the local load situation. Hence, comprehensive investigations on the mechanical deformation behaviour as well as the corresponding lifetime, based on experiments on the lamellar cast iron EN-GJL-300, were conducted within this thesis. These investigations cover quasi-static tensile tests, cyclic isothermal LCF-tests, non-isothermal TMF-tests at varying phase-shifts as well as cyclic creep experiments covering an operating temperature range of 25°C to 500°C. The identification of the locally dominating damage mechanisms as well as the interpretation of their interacting effect on fatigue was supported by an extensive damage analysis of the fractured specimens. It was found that the thermo-mechanical lifetime of lamellar cast iron is dominated by multiple mutual acting damage mechanisms, which interact with each other in a complex way. At this, the lifetime is especially affected by brittle damage parts at the graphite lamellas and the matrix material, but also by time-dependent creep effects as well as by classic fatigue damage. Consequently a methodology to simulate the complex deformation behaviour based on a damage modified viscoplastic constitutive model was derived from the experimental findings. This methodology also contains a semi-automated parameter optimization strategy featuring a genetic algorithm. The correspondingly conducted mechanical simulation runs correlate well with the experimental data. Only marginal deviations in the evaluated stress-strain hysteresis can be found at quite high temperatures. Finally, a phenomenological approach for lifetime estimation taking into account brittle damage in terms of cleavage fracture, creep effects as well as fatigue damage was derived according to the conducted fracture analysis. This advanced approach was validated for the lamellar cast iron EN-GJL-300, the vermicular EN-GJV-450 as well as the ductile cast iron EN-GJS-450 under the consideration of different in industries well established lifetime models. Thus, the phenomenological based model leads to a significant improvement for lamellar and vermicular cast iron regarding the deviation. As the model explicitly takes into account the local material damage due to brittle fracture, it is primarily designed for lamellar cast iron applications. By a modification based on the universal material law by Bäumel and Seeger the introduced model can be further extended to ductile cast irons, predicting the corresponding lifetime in an engineering acceptable deviation. Summing up, the developed approach significantly enhances the design procedure of thermo-mechanically loaded components made of stable solidified cast irons.