This study presents a novel approach to target pathological angiogenesis using engineered exosomes incorporating extremely small iron oxide nanoparticles (ESIONPs). The method utilizes macrophages as bioreactors to produce exosomes that are then modified with ESIONPs, resulting in ESIONPs@EXO. These exosomes exhibit magnetic imaging, ferroptosis-inducing, and immunotherapeutic properties. The study demonstrates that ESIONPs@EXO effectively suppresses pathological angiogenesis in vitro and in vivo without toxicity. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. The exosomes are derived from M1-polarized macrophages, which are known for their antiangiogenic and antitumor activity. The exosomes are capable of targeting pathological angiogenesis and exhibit excellent T1-weighted contrast properties for magnetic resonance imaging. The study also shows that ESIONPs@EXO can target pathological angiogenesis in vivo, including in models of oxygen-induced retinopathy and ocular melanoma. The exosomes are highly biocompatible and can target leaky pathological angiogenesis through intravenous administration, which could largely avoid the side effects resulting from repeated intravitreal injections. The results suggest that ESIONPs@EXO could be a promising nanoplatform for the treatment of pathological angiogenesis.This study presents a novel approach to target pathological angiogenesis using engineered exosomes incorporating extremely small iron oxide nanoparticles (ESIONPs). The method utilizes macrophages as bioreactors to produce exosomes that are then modified with ESIONPs, resulting in ESIONPs@EXO. These exosomes exhibit magnetic imaging, ferroptosis-inducing, and immunotherapeutic properties. The study demonstrates that ESIONPs@EXO effectively suppresses pathological angiogenesis in vitro and in vivo without toxicity. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. The exosomes are derived from M1-polarized macrophages, which are known for their antiangiogenic and antitumor activity. The exosomes are capable of targeting pathological angiogenesis and exhibit excellent T1-weighted contrast properties for magnetic resonance imaging. The study also shows that ESIONPs@EXO can target pathological angiogenesis in vivo, including in models of oxygen-induced retinopathy and ocular melanoma. The exosomes are highly biocompatible and can target leaky pathological angiogenesis through intravenous administration, which could largely avoid the side effects resulting from repeated intravitreal injections. The results suggest that ESIONPs@EXO could be a promising nanoplatform for the treatment of pathological angiogenesis.