Blood is vital fluid where cellular components are suspended within a non -cellular liquid matrix. The dysfunction or deficiency of these cellular components can cause serious morbidity and even mortality. Meanwhile, transfusion of blood components serves as a cornerstone during surgery, myelosuppression, and congenital disorders of the blood. However, donor-derived blood products are hindered by several challenges such as scarcity of supply, the requirement for matching, significant risks of pathogenic contamination, restricted shelf-life, and several other negative consequences. Currently, ongoing research focuses on addressing these issues, clinical interests have emerged in the bioengineering of artificial blood substitutes, aiming to mimic natural blood while avoiding the aforementioned concerns. Nanotechnology has offered innovative methods, including the development of synthetic red blood cells (RBCs) substitutes for oxygen transport, synthetic platelet substitutes for hemostasis, and synthetic white blood cells (WBCs) substitutes for immune responses. The study presents an overview of the role of nanotechnology in the production of synthetic blood substitutes, as well as an evaluation of the achievements and limitations of the existing state -of -the -art in this area. One area of research currently focuses on using cell culture technologies to make blood cells from stem cells, while another is investigating the use of nanotechnology to create blood cell replacements. In the near future, the product of ongoing research as well as comprehensive preclinical and clinical evaluations might lead to fully synthetic blood replacements for transfusion. Nanotechnology has offered a new perspective on the concept of artificial blood substitutes.