Direct metal laser sintering (DMLS) manufacturing method can be deployed for aerospace applications to realize advantages that are well documented. However, prior to their use in safety critical components, the failure mechanisms have to be well understood, especially for the unique defects in DMLS materials, such as porosity and residual stresses. In our work, fatigue crack initiation of a Ni-based superalloy, IN 718, produced by DMLS is studied. Microstructural features, such as grain size distribution, orientation distribution, presence of twins, voids, lead to heterogeneous deformation causing strain localization at certain locations where a fatigue crack is likely to initiate. A crystal plasticity based framework is developed to understand the dependence of microstructural attributes on mechanical behavior. 3D virtual microstructures are developed based on microstructure characterization and used within crystal plasticity simulations to understand crack initiation.