If structural reliability is estimated by following a strain-based approach, a material’s strength should be represented by the scatter of the e–N (E–N) curves that link the strain amplitude with the corresponding statistical distribution of the number of cycles-to-failure. The basic shape of the e–N curve is usually modelled by the Coffin–Manson relationship. If a loading mean level also needs to be considered, the original Coffin–Manson relationship is modified to account for the non-zero mean level of the loading, which can be achieved by using a Smith–Watson–Topper modification of the original Coffin–Manson relationship. In this paper, a methodology for estimating the dependence of the statistical distribution of the number of cycles-to-failure on the Smith–Watson–Topper modification is presented. The statistical distribution of the number of cycles-to-failure was modelled with a two-parametric Weibull probability density function. The core of the presented methodology is represented by a multilayer perceptron neural network combined with the Weibull probability density function using a size parameter that follows the Smith–Watson–Topper analytical model. The article presents the theoretical background of the methodology and its application in the case of experimental fatigue data. The results show that it is possible to model e–N curves and their scatter for different influential parameters, such as the specimen’s diameter and the testing temperature.