Hot work tool steels, which are used for the extrusion of non-ferrous metals, are exposed to high cyclic thermo-mechanical loads. Due to high production costs, a long lifetime is of high importance and, therefore, improvements in the microstructure are demanded. A reliable estimation of the service-lifetime of the tool is also essential. Presently, empirical approaches exist, such as the phenomenological Chaboche model, which is implemented in AbaqusTM. With this model, the inelastic strains in the tools can be calculated after the determination of the cyclic thermo-mechanical loads, which are simulated in DeformTM. The disadvantage of this approach lies in the fact that the parameters, which are required for the model, are only valid for a certain annealing condition of the material and a certain temperature range. Since the elastic-viscoplastic Chaboche model needs a large number of empirical parameters, which must be determined by extensive experimental methods, a simplification would be highly desirable. Therefore, the ambition in this work is to correlate the characteristics of the tool’s microstructure with the macroscopic material response. In order to realise such an idea, a physically based model is introduced, which should allow us to understand the reaction of the microstructure due to a thermo-mechanical load pattern, which occurs during an extrusion process. Three basic parameters are needed in this physical based approach, the conditions of the precipitates, the substructure, as well as the dislocation density. The model is based on a system of coupled differential equations, which calculates the evolution of the dislocation density due to the thermo-mechanical loading with the software MathCadTM. Hereby the initial substructure and the precipitation status are taken into account. The precipitation status is simulated using the thermo-kinetic software MatCalcTM. With this physically based modelling approach, the influence of a specific microstructure onto the material response due to service loads can be estimated. The results of both the phenomenological and the physically based approach can be compared by the inelastic strain value, which is an important output parameter in both approaches. Lifetime calculations were performed for different process conditions, and the service life of different tool steels was compared.