Cast steel components are affected by manufacturing process-based imperfections, which severely limit their fatigue strength. In this work, the linear-elastic strain energy density concept is applied to assess the fatigue behaviour of bulk defect-afflicted components made of high-strength cast steel alloy G12MnMo7-4+QT. Based on analytical calculations, an energy-based design limit curve is derived which merges experimental results of notched and unnotched small–scale specimens into a statistically proven scatter band. The stress ratio dependency is also investigated. Moreover, a numerical methodology is introduced, which facilitates the energy-based fatigue assessment of complex spatial imperfections on the basis of radiographs. Validation of the established framework utilizing experimental results of defect-afflicted large–scale specimens leads to sound accordance of numerically and experimentally derived fatigue strength values, showing an average deviation of about only eight percent.