Free flap tissue transfer is a cornerstone of modern reconstructive surgery, relying on the precise physiological interplay between vascular perfusion, tissue oxygenation, and cellular metabolism to achieve successful outcomes. This process involves the transfer of autologous tissue, along with its vascular supply, to a recipient site to restore form and function following trauma, oncologic resection, or congenital defects. The physiology of free flap transfer centres on the vascular anastomosis, which reestablishes blood flow, ensuring oxygen delivery and nutrient exchange necessary for cellular survival and repair. Key factors influencing flap viability include perfusion pressure, microvascular integrity, ischemia-reperfusion injury, and lymphatic drainage. Advances in monitoring technologies, such as laser Doppler flowmetry and near-infrared spectroscopy, have improved early detection of vascular compromise, facilitating timely intervention. This review highlights the physiological principles underlying free flap transplantation, explores the mechanisms of flap adaptation and integration, and discusses strategies to optimize outcomes, including preoperative conditioning, intraoperative techniques, and postoperative care. Understanding these physiological dynamics is essential for improving flap survival rates and advancing reconstructive surgical practice.