The article reviews the evidence for the use of tenecteplase as a thrombolytic agent in acute ischemic stroke (AIS). Tenecteplase, a genetically engineered mutant of tissue-type plasminogen activator (tPA), has shown potential advantages over alteplase, including better pharmacokinetics and pharmacodynamics, ease of administration, and improved recanalization and reperfusion without increased hemorrhagic risk. Clinical trials have demonstrated that tenecteplase is noninferior to alteplase and may even be superior in cases of large vessel occlusion (LVO). The 2023 European Stroke Organisation guidelines strongly recommend the use of 0.25 mg/kg tenecteplase as an alternative to 0.9 mg/kg alteplase for AIS within 4.5 hours of onset. Tenecteplase is also cost-effective, with significant savings compared to alteplase. Real-world studies suggest that tenecteplase is relatively effective and safe, with time-saving benefits. However, further research is needed to explore its use in extended time windows, minor strokes, and combination with endovascular therapy.The article reviews the evidence for the use of tenecteplase as a thrombolytic agent in acute ischemic stroke (AIS). Tenecteplase, a genetically engineered mutant of tissue-type plasminogen activator (tPA), has shown potential advantages over alteplase, including better pharmacokinetics and pharmacodynamics, ease of administration, and improved recanalization and reperfusion without increased hemorrhagic risk. Clinical trials have demonstrated that tenecteplase is noninferior to alteplase and may even be superior in cases of large vessel occlusion (LVO). The 2023 European Stroke Organisation guidelines strongly recommend the use of 0.25 mg/kg tenecteplase as an alternative to 0.9 mg/kg alteplase for AIS within 4.5 hours of onset. Tenecteplase is also cost-effective, with significant savings compared to alteplase. Real-world studies suggest that tenecteplase is relatively effective and safe, with time-saving benefits. However, further research is needed to explore its use in extended time windows, minor strokes, and combination with endovascular therapy.