Purpose: to structure the organizational problems of regional organ donation and transplantation systems and identify key tasks for their optimization. Materials and Methods. To achieve the stated objective, this study employed general scientific methods such as analysis, synthesis, generalization, interpretation of scientific data, as well as systemic and structural-functional approaches. Results. Transplantation is a critically important part of treating individuals with damaged or dysfunctional organs or tissues. It holds global medical and social significance. The primary challenge in transplantation is the shortage of donor organs The main issue in organ transplantation, the problem of an adequate supply of optimal donor organs, can be addressed through effective organization of the donation process. The progress of transplantology is directly dependent on the level of organization of the transplantation process, and therefore, the best results in transplant activity are achieved by countries that have managed to establish an efficient transplant coordination system. Transplantology serves as a growth point for the entire healthcare system. The conducted research has shown that the key problems defining the directions for optimizing the regional organ donation and transplantation system include the following. In the systemic regional model of organ donation and transplantation, it is important to establish a mechanism for patient transfer from donor bases of regional transplantation centers, control organ allocation, and introduce modern medical technology standards at all stages of the donation process to optimize the diagnostic and therapeutic process. Conclusions. The article presents the structured key problems of optimizing the organ donation and transplantation system in the regions of Ukraine and defines optimization tasks as a framework for building a modern regional system. The identified problems confirmed that the conditions in which health care providers conduct transplants work, increasing the volume of transplants that contribute to the preservation of public health, and often life, is problematic. The study contributed to the formation of priority are as for the development of regional health care providers conducting organ transplantation.