 Cancer stem cells, CSCS, play a significant role in tumor initiation, growth, metastasis, immunovation, and therapy resistance by interacting with the tumor microenvironment, TME, which provides a supportive niche for CSC survival and self-renewal while CSCS influence the polarization and persistence of the TME. Novel therapeutic approaches that specifically target CSCS and the TME hold promise for future clinical and translational studies in cancer treatment. This article was authored by Yang Ruoda Li, Ying Fang, Zabai Liu, and others.