The design and production of light structures in cast iron with high static and fatigue performance is of major interest in e.g. the automotive area. Since the casting process inevitably leads to heterogeneous solidification conditions and variations in microstructural features and material properties, the effects on multiple scale levels needs to be considered in the determination of the local fatigue performance. In the current work, microstructural features of different cast irons are captured by use of micro X-ray tomography, and 3D finite element models generated. The details of the 3D microstructure differ from the commonly used 2D representations in that the actual geometry is captured and that there is not a need to compensate for 3D-effects. The first objective with the present study is to try and highlight certain aspects at the micro scale that might be the underlying cause of fatigue crack initiation, and ultimately crack propagation, under fatigue loading for cast iron alloys. The second objective is to incorporate the gained knowledge about the microstructural behavior into multi-scale simulations at a structural length scale, including the local damage level obtained in the heterogeneous structure subjected to fatigue load.