During the casting process and solidification of ductile iron castings, a heterogeneous microstructure is formed throughout the casting. This distribution is strongly influenced by the item geometry and the process related factors, as chemical composition and local solidification conditions. Geometrical changes to the geometry of the casting thus alters the local mechanical behavior and properties, as well as the distribution of stresses and strains when the casting is subjected to load. In order to find an optimal geometry, e.g. with reduced weight and increased load-bearing capacity, this interdependency between geometry and local material behavior needs to be considered and integrated into the optimization method. In this contribution, recent developments in the multidisciplinary integration of casting process simulation, solidification and microstructure modelling, microstructure-based material characterization, finite element structural analyses with local material behavior and structural optimization techniques are presented and discussed. The effect and relevance of considering the local material behavior in shape optimization of ductile iron castings is discussed and evidenced by an industrial application. It is shown that by adopting a multidisciplinary optimization approach by integration of casting simulation and local material behavior into shape optimization, the potential of the casting process to obtain components with high performance and reliability can be enabled and utilized.