| Cancer stem cells (CSCs) are a crucial subpopulation of cells responsible for tumor drug resistance, recurrence, and metastasis, and they are difficult to eradicate with conventional therapies. Traditional Chinese medicine (TCM), grounded in the holistic concept of “strengthening vital qi and eliminating pathogens” (Fuzheng Quxie), offers unique advantages in modulating the tumor microenvironment and enhancing systemic immunity. This article systematically reviews the research progress of TCM in targeting CSCs. Studies have demonstrated that active TCM ingredients (e.g., ginsenosides, curcumin, berberine, resveratrol, and evodiamine) and compound formulas (e.g., Sijunzi Decoction, Jiedu Xiaozheng Decoction, and Biejiajian Pill) can intervene through multiple targets in signaling pathways such as Wnt/β-catenin, Notch, Hedgehog, and STAT3, thereby inhibiting CSCs self-renewal, stemness marker expression, and drug resistance, and synergistically enhancing the efficacy of conventional treatments. According to TCM theory, CSCs are categorized as excessive pathogenic factors such as “phlegm turbidity,” “latent toxin,” and “blood stasis.” The pathogenesis emphasizes the lingering of pathogens due to deficient healthy qi caused by spleen and kidney deficiency, and the therapeutic principle focuses on the combination of resolving phlegm, removing toxin, and eliminating blood stasis with invigorating the spleen and tonifying the kidney. Future research should integrate single-cell technologies, nano-delivery systems, and high-quality clinical trials to deeply elucidate the mechanisms by which TCM regulates CSCs, thereby providing new strategies for cancer treatment with integrated traditional Chinese and Western medicine. |