Fatigue as the most frequent mode of failure among mechanical systems has been the focus of a large part of the research community. Modern manufacturing technologies are developed to address the need for complex geometries of parts used in industrial applications and reduce the associated cost of manufacturing and post manufacturing processes. Additively manufactured parts, due to their surface roughness and volumetric defects, are very sensitive to cyclic loading. Fatigue of AM parts, due to their complexity, has brought multiple disciplines such as mechanical engineering, materials science, and physics together. Various materials have been developed to suit specific purposes and withstand extreme conditions. With the advancement of numerical models and computational capabilities, the deformation mechanisms that are involved in the process leading to fracture have been investigated at multiple length scales. In this dissertation, a comprehensive numerical multiscale investigation of phenomena affecting the fatigue performance of additively manufactured metallic materials, specifically nickel superalloys, has been conducted. At a lower length scale, the intrinsic properties of the material, such as fault energies, are calculated in the disordered solid solution matrix and the ordered strengthening precipitates using density functional theory. The operation of persistent slip bands formed during cyclic loading is studied using molecular dynamics to further understand the parameters affecting dislocation glide. The energetic properties and strength of metal/metal and metal/ceramic interfaces as an important microstructural feature are studied in detail. Mechanisms responsible for deformations at such locations are illustrated. At the continuum level, crystal plasticity analysis is done to understand the effect of the surface hard coating applied to the parts and components to suppress the formation of surface extrusions and prevent the formation of cracks. Lastly, a crystal plasticity hardening model has been proposed that can capture a location-dependent slip resistance evolution. The formation of persistent slip bands and strain localizations as a result of cyclic deformation is studied. Using this model, the initiation behavior of cracks within the material is investigated in detail.