The goal of this study is to investigate the microstructure and microstructure-based fatigue (MSF) model of additively-manufactured (AM) metallic materials. Several challenges associated with different metals produced through additive manufacturing (Laser Enhanced Net Shaping – LENS®) have been addressed experimentally and numerically. Significant research efforts are focused on optimizing the process parameters for AM manufacturing; however, achieving a homogenous, defectree AM product immediately after its fabrication without postabrication processing has not been fully established yet. Thus, in order to adopt AM materials for applications, a thorough understanding of the impact of AM process parameters on the mechanical behavior of AM parts based on their resultant microstructure is required. Therefore, experiments in this study elucidate the effects of process parameters – i.e. laser power, traverse speed and powder feed rate – on the microstructural characteristics and mechanical properties of AM specimens. A majority of fatigue data in the literature are on rotation/bending test of wrought specimens; however, few studies examined the fatigue behavior of AM specimens. So, investigating the fatigue resistance and failure mechanism of AM specimens fabricated via LENS® is crucial. Finally, a microstructure-based MultiStage Fatigue (MSF) model for AM specimens is proposed. For calibration of the model, fatigue experiments were exploited to determine structure-property relations for an AM alloy. Additional modifications to the microstructurally-based MSF Model were implemented based on microstructural analysis of the fracture surfaces – e.g. grain misorientation and grain orientation angles were added to the MSF code.