Triple-negative breast cancer (TNBC) is a broad collection of breast cancer that tests negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein. TNBC is considered to have poorer prognosis than other types of breast cancer because of a lack of effective therapeutic targets. The success of precision cancer therapies relies on the clarification of key molecular mechanisms that drive tumor growth and metastasis; however, TNBC is highly heterogeneous in terms of their cellular lineage composition and the molecular nature within each individual case. In particular, the rare and sometimes slow cycling cancer stem cells (CSCs) can provide effective means for TNBC to resist various treatments. Single cell analysis technologies, including single-cell RNA-seq (scRNA-seq) and proteomics, provide an avenue to unravel patient-level intratumoral heterogeneity by identifying CSCs populations, CSC biomarkers and the range of tumor microenvironment cellular constituents that contribute to tumor growth. This review discusses the emerging evidence for the role of CSCs in driving TNBC incidence and the therapeutic implications in manipulating molecular signaling against this rare cell population for the control of this deadly disease.