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The fracture behavior of the Ti–Al alloy is significantly affected by its nano-lamellar structure. However, further investigation is still required to fully comprehend how the initial crack configuration influences the lamellar Ti–Al's deformation behavior. Although molecular dynamics simulations are a great way to study crack-tip interactions in interface-dominated microstructures, the design of the simulation can have an impact on the behavior that is predicted. To shed light on this matter and at the same time to understand the impact of the specific interface structure, a systematic study of crack-tip interface interactions in nano-lamellar two-phase Ti–Al was carried out. The type of interface and crack configuration were varied in these simulations to distinguish between the effects of the microstructure and the crack geometry. Results show that the semi-coherent pseudo twin (γ/PT) interface is the strongest barrier for crack propagation while the coherent true twin interface (γ/TT) is the weakest. After a thorough review of the contributing factors, it is evident that the orientation of the crack has a greater impact on its propagation than the aspect ratio of the crack. The stress shielding effectiveness of lamellar interfaces is strongly dependent on the crack configuration. However, regardless of the initial crack set-up, the coherent TT interface appears to be the most effective interface in terms of shielding.