Stroke ranks among the leading causes of global disease burden, injury, and risk factors, with acute ischemic stroke (AIS) accounting for approximately 75% of cases. Intravenous thrombolysis stands as one of the most effective treatments for AIS, enabling rapid recanalization of occluded vessels and restoration of blood flow to minimize disability or mortality risks in patients. In recent years, novel intravenous thrombolytic agents with favorable safety profiles and distinct therapeutic benefits have gained significant attention. This review systematically summarizes evidence from multicenter studies and explores potential mechanisms underlying three such drugs—prourokinase, reteplase, and tenecteplase—aiming to provide theoretical support for advancing clinical research and deepening insights into their mechanisms of action.