Leukemia  remains  a  significant  clinical  challenge  despite  advances  in  chemotherapy,  targeted  therapies.  Stem  cell–based 
therapies  represent  a  cornerstone  in  the  treatment  of  leukemia,  offering  the  potential  for  both  curative  and  regenerative 
outcomes. Hematopoietic stem cell transplantation (HSCT) remains the most effective and widely used therapeutic approach, 
capable of restoring normal hematopoiesis following intensive chemotherapy or radiotherapy. Recent advances in stem cell 
biology and genetic engineering have further expanded the landscape of leukemia treatment. Induced pluripotent stem cells 
(iPSCs)  and  mesenchymal  stem  cells  (MSCs)  are  being  explored  for  their  roles  in  disease modeling,  drug  screening,  and  as 
supportive agents to enhance engraftment and reduce transplant-related complications. This review provides a comprehensive 
overview  of  leukemia and  its current  therapeutic approaches,  and examines  the  role of  stem  cells  in modulating  malignant 
hematopoiesis. Evidence from preclinical and clinical studies demonstrates that stem cells, particularly MSCs, hematopoietic 
stem cells (HSCs), and umbilical cord–derived or Wharton’s jelly–derived stem cells, can exert anti-leukemic effects through 
mechanisms  such  as  apoptosis  induction,  cell  cycle  arrest,  and  modulation  of  the  bone  marrow  microenvironment.  The 
therapeutic potential of stem cells is explored in the context of major leukemia subtypes, acute myeloid leukemia (AML), acut e 
lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), highlighting both  in 
vitro  and  in  vivo  findings,  including  clinical  trial  evidence.  Furthermore,  emerging  therapeutic  directions  are  discussed, 
including the use of stem cells as drug delivery vehicles, gene therapy carriers, and sources of extracellular vesicles, alon gside 
strategies to disrupt leukemic stem cell niches and enhance chemotherapy efficacy. While stem cell–based interventions hold 
considerable  promise,  their  dualistic  effects  on  tumor  progression,  context-dependent  outcomes,  and  safety  concerns 
underscore the need for further mechanistic studies and carefully designed clinical trials. Collectively, this review emphasizes 
the evolving  role  of  stem  cell–based  therapies  in  leukemia management  and  identifies  future  directions  for  optimizing  their 
clinical application toward long-term disease control and improved patient outcomes.