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The current review aims to provide a current landscape and future trends of biomimetic nanoparticles which have the potential to revolutionize the field of transplantation in the next decade.Currently, the inability to safely induce robust donor-specific immunological tolerance makes it difficult to achieve immunosuppression-free graft survival. Despite progresses in the development of nanotherapeutics for antigen-specific immunomodulation in autoimmune diseases and in cancer treatments, few have been proposed and tested in transplantation with success. The complexity of parallel rejection mechanisms, multitude of antigen epitopes, and potential epitope spreading have challenged conventional nanodelivery systems in transplant models. Overcoming such challenges, biomimetic nanotherapeutics represent a promising alternative, as they allow better recapitulation of the complexity of the main biological players involved in tolerance. Within biomimetic nanodelivery systems, we envision that hybrid systems mimicking extracellular vesicles have the potential to bridging the gap between cell-based therapies, which are effective but costly and difficult to translate in clinical practice, and fully synthetic systems which are relatively easy to manufacture but lack the capacity to recapitulate the complexity of transplant antigens and tolerance mechanisms.Next-generation nanotherapeutics for tolerance delivery is evolving toward biomimetic systems capable of capturing an increasing level of antigen complexity and exploiting multiple tolerance pathways.