Ultrasound has been widely used as an external stimulus to trigger drug release from nanomaterials in thrombosis treatment. Here, we introduce a novel strategy leveraging nanomaterials not for drug delivery, but for enhancing US-induced thrombolysis. This innovative strategy is particularly significant, as thrombolytic drugs inherently pose a risk of systemic bleeding. We combined branched silver-iron oxide nanoparticles (AgIONPs) with low-intensity focused ultrasound to evaluate their thrombolytic potential. Binding assays in in vitro human blood clots and in a thrombosis mouse model confirmed that the targeted AgIONPs specifically bound to thrombi. Upon ultrasound activation, AgIONPs facilitated thrombolysis via two key mechanisms: hyperthermia driven by the nanoparticle-mediated thermal conversion, and mechanical shear forces induced by ultrasound. The combination of AgIONPs and US generated a synergistic thrombolytic effect, demonstrating significant efficacy in both <i>in vitro</i> and <i>in vivo</i>.