<p>Pores are inevitable defects in additively manufactured nickel-based alloys, and under cyclic loading they readily trigger component failure, thereby severely limiting the service performance of such alloys. In this study, an advanced mesoscale model for crack initiation and propagation associated with pore defects is developed by integrating crystal plasticity finite element modeling with continuum damage mechanics, systematically elucidating the fatigue failure mechanisms induced by pores. The results reveal that the crack path is governed by the coupled effects of pore morphology, location, size, and grain-level slip activity. When the plane of the most activated slip system is parallel to the grain boundary, intergranular propagation dominates; otherwise, transgranular cracking occurs. The presence of pore defects markedly accelerates crack growth, with larger pores leading to faster propagation rates. Variations in pore shape and position influence the surrounding grain structure and dislocation density, thereby altering both crack initiation sites and propagation trajectories. Lateral pore offsets exhibit a more pronounced influence on crack deflection compared to vertical offsets. Moreover, crack deflection occurs only when the actual distance between the crack tip and the pore center falls below a critical threshold. This threshold enables the classification of the crack-affected domain into three zones: the crack initiation zone, the deflection zone, and the weakly affected zone, each exhibiting distinct distributions of stored energy density and slip activity.</p>