FOXM1 is an oncogenic transcription factor that promotes tumor growth, metastasis, and progression of drug resistance, and its high expression correlates with poor patient survival across various solid tumors. Mutations in the p53 tumor suppressor, a common genetic alteration in approximately half of the human tumors, lead to FOXM1 overexpression. Emerging evidence indicates that a small subpopulation of cancer cells, cancer stem cells (CSCs), within tumors contributes to relapse, metastasis, and progression due to their roles in tumor initiation, self-renewal, differentiation, and therapy resistance. The clinical significance of CSCs on patient prognosis underscores the need for CSC-targeted therapies. FOXM1 plays a significant role in CSC-proliferation and survival, interacting with key stemness-related and pluripotency-associated transcription factors such as SOX2, OCT4, NANOG, and stem cell markers CD133, CD44, CD24, and ALDH. Notably, in-vivo genetic targeting of FOXM1 has been shown to block tumor growth in experimental models. However, there is currently no FDAapproved therapy specifically targeting FOXM1. Given its pivotal role, developing FOXM1-targeted therapies holds significant potential to overcome therapy resistance, halt cancer progression, and improve patient survival. This review evaluates the latest data on the role of FOXM1 in CSCs and explores potential strategies for targeting FOXM1 as a therapeutic approach.