The presence of inclusions is a known source of crack initiation and component failure in cast materials. In this work, the role of inclusions is investigated via a combined program of high-temperature low-cycle fatigue testing and computational modelling of a tempered martensitic steel, MarBN. Microstructural analysis has shown that manufacturing-induced oxide inclusions are a key source of fatigue crack initiation. A fully coupled, critical plane life prediction and damage model is implemented in a unified cyclic viscoplastic user-material subroutine and applied to predict damage and micro-crack initiation for inclusions. It is deduced that more careful control of the development of inclusions in the manufacturing process will provide enhanced material and component performance for highly flexible and ultrasupercritical plant conditions.