Exosomes are lipid bilayer vesicles approximately 30–150 nm in diameter that serve as key mediators of intercellular communication. By transporting diverse bioactive molecules, including proteins and nucleic acids, they play a crucial role in tumor initiation and progression. Among their functional cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and intercellular signaling, significantly influencing tumor biology. This review provides a comprehensive overview of the multifaceted roles of exosomal miRNAs in remodeling the tumor microenvironment (TME) and regulating cancer stem cells (CSCs). Specifically, exosomal miRNAs modulate various immune cells (such as macrophages, T cells, and NK cells) as well as cancer-associated fibroblasts (CAFs), thereby promoting immune evasion, angiogenesis, epithelial–mesenchymal transition (EMT), and metastatic progression. At the same time, they enhance CSC stemness, self-renewal, and therapeutic resistance, ultimately driving tumor recurrence and dissemination. Furthermore, exosome-mediated miRNA signaling acts as a critical force in malignant progression. Finally, we discuss the clinical potential of exosomal miRNAs as diagnostic and prognostic biomarkers, therapeutic targets, and vehicles for targeted drug delivery, highlighting their translational value and future directions in cancer research.

Exosomes are lipid bilayer vesicles measuring 30–150 nm in diameter that serve as crucial mediators of intercellular communication. By transporting bioactive molecules such as proteins and nucleic acids, they play a pivotal role in cancer progression. Among their cargo, exosomal microRNAs (miRNAs) are central to epigenetic regulation and signal transduction. Cancer stem cells (CSCs), a distinct subpopulation with self-renewal and multi-lineage differentiation capabilities, drive tumor initiation, metastasis, and recurrence, making them critical therapeutic targets. This review systematically summarizes the regulatory mechanisms of exosomal miRNAs in tumorigenesis, metastasis, and drug resistance, with a particular focus on their roles in maintaining CSC properties and promoting therapy resistance. We further discuss their clinical potential as liquid biopsy biomarkers and therapeutic targets. Finally, we outline current research limitations and future directions to advance precision oncology.