Intravenous thrombolysis is a widely used treatment for acute ischaemic stroke (AIS), yet recanalization rates remain limited and many patients subsequently undergo mechanical thrombectomy (MT) [1]. While thrombolysis is often modelled primarily as a biochemical fibrinolysis process [2], growing experimental evidence indicates that it also induces substantial changes in clot mechanical behaviour, which can strongly influence clot–flow interaction and downstream endovascular treatment. This work builds on experimental investigations that quantify how recombinant tissue plasminogen activator (r-tPA) alters clot mechanical properties across a range of physiologically relevant thrombus compositions. Mechanical testing demonstrated that exposure time to r-tPA, rather than dose, is the dominant predictor of reduced clot stiffness and viscoelastic energy dissipation, even in the absence of large reductions in clot mass, indicating that partial fibrin cleavage can significantly weaken mechanical integrity prior to complete lysis [3]. Complementary in-vitro thrombolysis experiments conducted under physiological flow further showed that clot composition and vessel compliance govern clot motion, deformation, and fragmentation, with RBC-rich clots exhibiting increased oscillatory behaviour and accelerated size reduction compared with fibrin-rich clots [4]. Together, these results highlight thrombolysis as a mechanically active process in which evolving clot elasticity and viscoelastic response modulate flow penetration, hydrodynamic loading, and clot stability. Such effects are difficult to capture using conventional modelling assumptions that neglect clot deformation and motion, yet they are directly relevant to MT, where thrombolysis-induced softening may either facilitate device engagement or increase the risk of clot migration and fragmentation [5,6]. Motivated by these experiments and prior experience with both three-dimensional and reduced-order modelling approaches, future work will focus on developing efficient two-dimensional computational models, enabling investigation of lysis speed under varying haemodynamic conditions. This framework will allow systematic exploration of the effects of collateral flow pathways, clot structure, and fragmentation on thrombolysis outcomes, while remaining significantly more time-efficient and robust than fully resolved three-dimensional simulations. Planned validation will include bench-top experiments in transparent models.