Venetoclax, the first selective inhibitor of B-cell lymphoma 2 (BCL-2), has demonstrated remarkable therapeutic efficacy in the treatment of various hematologic malignancies.However, the emergence of drug resistance during clinical application has limited the durability of its efficacy and adversely affected patient prognosis. In recent years, accumulating evidence has revealed that exosomes, as critical mediators of intercellular communication, play a pivotal role in the development of venetoclax resistance. Exosomes can transport bioactive molecules, including proteins,microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), thereby regulating apoptotic signaling pathways, mediating metabolic reprogramming, promoting drug efflux, and inducing remodeling of the tumor microenvironment. Through these mechanisms, exosomes enhance tumor cell survival and allow evasion of venetoclax-induced apoptosis. This review systematically summarizes the latest advances in exosome-mediated mechanisms of venetoclax resistance, aiming to elucidate the network-based regulatory mechanisms underlying resistance development, help reverse drug resistance and restore drug sensitivity, and provide theoretical foundations and research directions for the development of exosome-targeted therapeutic strategies.