A comprehensive review of tenecteplase for thrombolysis in acute ischemic stroke highlights its potential as an alternative to alteplase. Tenecteplase has favorable pharmacokinetic and pharmacodynamic properties, including a longer half-life, higher fibrin specificity, and lower risk of intracranial hemorrhage. Clinical trials show that tenecteplase is not inferior to alteplase and may even be superior in cases of large vessel occlusion. It is easier to administer, reducing the risk of medication errors and improving interhospital transfer efficiency. Recent trials, including AcT, TRACE-2, and ATTEST-2, support the use of 0.25 mg/kg tenecteplase as an alternative to 0.9 mg/kg alteplase within 4.5 hours of symptom onset. The 2023 European Stroke Organisation guideline and the UK/ Ireland stroke guideline recommend tenecteplase for acute ischemic stroke. Animal studies also demonstrate tenecteplase's advantages in pharmacodynamics and pharmacokinetics, including reduced bleeding and improved clot lysis. Phase 3 trials confirm tenecteplase's noninferiority to alteplase in terms of efficacy and safety, particularly in patients with large vessel occlusion. Real-world data show that tenecteplase is effective and safe, with time-saving benefits. Economic analyses indicate significant cost savings when switching to tenecteplase. However, further research is needed to explore its use in extended time windows, minor strokes, and prehospital settings. Overall, tenecteplase is a promising alternative to alteplase for thrombolysis in acute ischemic stroke.A comprehensive review of tenecteplase for thrombolysis in acute ischemic stroke highlights its potential as an alternative to alteplase. Tenecteplase has favorable pharmacokinetic and pharmacodynamic properties, including a longer half-life, higher fibrin specificity, and lower risk of intracranial hemorrhage. Clinical trials show that tenecteplase is not inferior to alteplase and may even be superior in cases of large vessel occlusion. It is easier to administer, reducing the risk of medication errors and improving interhospital transfer efficiency. Recent trials, including AcT, TRACE-2, and ATTEST-2, support the use of 0.25 mg/kg tenecteplase as an alternative to 0.9 mg/kg alteplase within 4.5 hours of symptom onset. The 2023 European Stroke Organisation guideline and the UK/ Ireland stroke guideline recommend tenecteplase for acute ischemic stroke. Animal studies also demonstrate tenecteplase's advantages in pharmacodynamics and pharmacokinetics, including reduced bleeding and improved clot lysis. Phase 3 trials confirm tenecteplase's noninferiority to alteplase in terms of efficacy and safety, particularly in patients with large vessel occlusion. Real-world data show that tenecteplase is effective and safe, with time-saving benefits. Economic analyses indicate significant cost savings when switching to tenecteplase. However, further research is needed to explore its use in extended time windows, minor strokes, and prehospital settings. Overall, tenecteplase is a promising alternative to alteplase for thrombolysis in acute ischemic stroke.