For the design of thick-walled nodular cast iron components, fatigue assessment, especially in the context of local imperfections in the material, is a challenging task. Not only the cyclic material behavior of the sound baseline material, but also the cyclic behavior of materials with imperfections, such as shrinkages, dross and chunky graphite, needs to be considered during the design process of cast iron components. In addition to this, new materials, such as solid solution strengthened alloys, offer new possibilities in lightweight design, but need to be assessed concerning their fatigue strength and elastic-plastic material behavior. If a safe and reproducible fatigue assessment for any component cannot be performed and a secure usage is therefore not given, the cast components are generally rejected, leading to a loss of additional material, energy and money for recasting the component. In this context, four nodular cast iron materials are compared with reference to their cyclic material and fatigue behavior as well as their potential for a lightweight design, based on stress- and strain-controlled tests both for sound and defective material. However, to develop an optimal and individual fatigue design method for cast components with local material imperfections present, the component’s local fatigue strength needs to be combined with information from non-destructive testing (NDT), since a removal of specimens is generally not possible. For this purpose, as an example, a method is described that uses information from ultrasonic and X-ray analysis as well as the given fatigue strength of the baseline material to conduct a fatigue assessment of local shrinkages in nodular cast iron components. The method is based on the reproducible measurement of the local density by NDT and its correlation with the local fatigue notch factor, enabling a safe and local assessment of the allowable fatigue strength when shrinkages are present.