Purpose <p>This review explores the pivotal role of haematopoietic cell transplantation (HCT) within the landscape of translational medicine. The primary objective is to examine how breakthroughs in stem cell biology, conditioning protocols, immune regulation, and gene editing strategies have transformed HCT into a highly adaptable therapeutic option for both malignant and non-malignant disorders.</p> Methods <p>An extensive literature review was conducted, focusing on studies published between 2015 and 2025, using databases such as PubMed, Web of Science, and Scopus. Selected peer reviewed articles were systematically categorized into key thematic areas: stem cell sources, conditioning regimens, immune management (particularly graft versus host disease), and genetic modification techniques in transplantation. Both clinical trials and experimental research were critically analyzed to identify key developments and ongoing challenges.</p> Results <p>Expansion of donor availability particularly through haploidentical and umbilical cord blood sources has significantly broadened patient access to transplantation. The use of reduced intensity conditioning has allowed safer procedures for elderly and comorbid patients. Innovations in immunomodulation have enhanced control over GVHD while preserving anti-tumor effects. Furthermore, gene editing technologies applied to autologous transplants are showing encouraging outcomes in treating genetic disorders. Despite these strides, issues such as disease relapse, transplant related complications, and financial limitations continue to pose challenges.</p> Conclusion <p>Once considered experimental, HCT has become a foundational therapy in contemporary medicine. Ongoing advances in cellular engineering and supportive strategies are central to its evolution as a personalized and regenerative treatment modality.</p> Lay Summary <p>Haematopoietic Cell Transplantation (HCT) is a vital therapeutic strategy for treating blood cancers, immune deficiencies, and genetic disorders. This review outlines the evolution, types, and biological basis of HCT, including autologous, allogeneic, and haploidentical transplants. It examines pre transplant conditioning, immunological challenges like graft versus host disease, and clinical applications. Advances in personalized medicine, such as genomic profiling and biomarker guided therapies, are improving outcomes. Emerging innovations like gene editing and immune engineering further enhance HCT’s potential. The review also highlights current challenges and future directions to optimize safety, effectiveness, and broader accessibility of this life saving procedure.</p> Graphical Abstract <p></p>