Thromboembolic diseases such as acute ischemic stroke, pulmonary embolism, deep vein thrombosis, and myocardial infarction are among the leading causes of death and long-term disability worldwide. In many of these conditions, the immediate problem is simple in principle: a blood clot blocks flow. However, the clot itself is not so simple. Its composition and internal architecture can vary widely across patients and even within the same thrombus, which makes treatment response difficult to anticipate. Mechanical thrombectomy, a minimally invasive catheter-based procedure that removes the clot from the vessel, has dramatically improved outcomes for many stroke patients. Still, thrombectomy does not work equally well for all cases. Some clots are retrieved in one pass, while others deform, fragment, or resist removal, increasing procedure time and the risk of distal embolization or incomplete reperfusion. A key reason is that thrombus microstructure – how red blood cells, fibrin, and platelet are arranged – strongly influences thrombus mechanics. That mechanical behavior, in turn, is a major determinant of what happens during device–clot interaction and ultimately whether the treatment succeeds. To bridge the gap between what we can see clinically and what controls mechanical response, we developed a thrombus digital twin that explicitly represents different tissue components and their structural organization. Rather than treating the clot as a uniform material, the model incorporatesmicrostructure-informed constitutive behavior and fracture, allowing us to probe how changes in composition, heterogeneity, and fiber organization translate into macroscale deformation and failure. This provides a virtual testbed to study why two thrombi that look similar on imaging can behave very differently during intervention, and to explore which microstructural signatures are most predictive of procedural outcome. In this talk, I will show how the thrombus microstructure shapes thrombus stiffness and deformability, drives fracture and fragmentation under thrombectomy-like loading, and leaves measurable fingerprints in clinical imaging. Together, these results point toward a more mechanistic and patient-specific view of thrombectomy—where imaging-informed microstructure helps explain failure modes and guides better treatment planning and device design.