The ongoing studies of the influence of internal defects on fatigue strength of additively manufactured metals adopted an internal crack or notch-like model at which the threshold stress intensity factor is the driving mechanism of fatigue failure. The current article highlights a shortcoming of this approach and offers an alternative based on X-ray microcomputed tomography and cyclic plasticity with a hybrid formulation of Chaboche and Armstrong–Frederick material laws. The presented tessellation and geometrical transformation scheme enabled a significantly more realistic morphological representation of internal defects that yielded a cyclic strain within 2% of the experimental values. This means that cyclic plasticity models have an accurate prediction of mechanical properties without repeating a full set of experiments for additively manufactured arbitrary microstructures. The coupling with a material law that is oriented towards the treatment of cyclic hardening and softening enabled more accurate computation of internal stresses under cyclic loading than ever before owing to the maturity of tessellation and numerical tools since then. The resulting stress–strain distributions were used as input to the Fatemi–Socie damage model, based on which a successful calculation of fatigue lifetime became possible. Furthermore, acting stresses on the internal pores were shown to be more than 450% concerning the applied remote stress amplitude. The results are a pretext to a scale bridging numerical solution that accounts for the short crack formation stage based on microstructural damage.