Cancer has long been one of the major diseases threatening human health. Despite significant achievements in cancer treatment, cancer recurrence and metastasis remain the primary causes of high mortality rates among clinical patients. While chemotherapy and radiation therapy continue to be the mainstay of clinical cancer treatment, drug resistance persists, leading to cancer relapse and poor prognosis. A wealth of literature indicates a strong correlation between drug resistance and cancer stem cells (CSCs). Cancer stem cells, also known as tumor-initiating cells, constitute a small subset of malignant tumor cells. They exhibit characteristics of both stem cells and cancer cells, including self-renewal and differentiation properties. Despite their small proportion within tumor tissue, tumor stem cells are considered culprits in tumorigenesis, treatment resistance, metastasis, and relapse. Advances in cell biology have revealed several mechanisms through which tumor stem cells acquire resistance to chemotherapy and radiotherapy. These mechanisms include elevated levels of ATP-binding cassette (ABC) transporters, exceptional DNA repair capacity, overexpression of antiapoptotic proteins, and enhanced protection against reactive oxygen species (ROS). Furthermore, tumor stem cells maintain their stem cell properties by overactivating various transcription factors and signaling pathways, such as Wnt/β-catenin, Notch, Hedgehog, and Nanog. This self-renewal and proliferation of tumor stem cells contribute to tumor progression. Typically, CSCs are implicated in treatment failure, relapse, and metastasis due to their stem-like characteristics. Consequently, targeting CSCs represents an effective anticancer therapeutic strategy. Currently, several strategies have been developed to eradicate cancer stem cells (CSCs), including targeting CSC surface markers, inhibiting ATP-binding cassette transporters, intervening in critical signaling pathways, and inducing differentiation of tumor stem cells. Additionally, phototherapy (both photodynamic therapy and photothermal therapy), as a noninvasive and spatiotemporally controlled approach, achieves indiscriminate killing of tumor cells and tumor stem cells by converting light into heat or reactive oxygen species. Consequently, it serves as an alternative method for eliminating tumor stem cells. Furthermore, recent literature suggests that tumor stem cells exhibit significant sensitivity to ferroptosis, making ferroptosis another viable approach for eradicating tumor stem cells.