Material inhomogeneities that occur across multiple length scales frequently impact metallic materials manufactured by additive methodologies. Both geometrical irregularities and non-metallic inclusions — often referred to as defects — can markedly degrade the fatigue performance of the manufactured material, particularly if no further post-processing is applied. As such, incorporating these defects into analyses is critical for an accurate evaluation of the material’s structural integrity. Fracture Mechanics-based approaches have proven effective in addressing bulk and sub-surface defects; however, a consensus has yet to be reached on the most effective method for addressing surface geometrical inhomogeneities (e.g., surface roughness). This talk presents the effectiveness of a generalised defect-based model capable of accounting for bulk, sub-surface, and surface roughness effects. The model was calibrated based on a detailed experimental fatigue characterisation study of a Ti-6Al-4V alloy manufactured through two different techniques, i.e., Electron Beam Melting (EBM) and Selective Laser Melting (SLM). To achieve varied defect characteristics and quantitatively assess their influence on fatigue, the additively manufactured materials were subjected to different combinations of post-processing (e.g., Hot Isostatic Pressing, in-vacuum Heat Treatment). This methodology proved effective across all examined material conditions, enabling a probabilistic evaluation of fatigue failure performance.