Newly emerging technologies are rapidly changing conventional approaches to organ transplantation. In the modern era, the key challenges to transplantation include (1) how to best individualize and possibly eliminate the need for life-long immunosuppression and (2) how to expand the donor pool suitable for human transplantation. This article aims to provide readers with an updated review of three new technologies that address these challenges. First, single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to transplantation. The new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants, as well as exciting new molecular signatures involved in alloimmune responses. Second, sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant tolerance. Tolerogenic nanoparticles with regulatory molecules and donor antigens are capable of targeting host immune responses with tremendous precision, which, in some cases, results in donor-specific tolerance. Third, CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory molecules. This technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human organs. Collectively, these new technologies are positioning the transplant community for major breakthroughs that will significantly advance transplant medicine.