By 2050, organ transplantation will be radically transformed—from a scarce, donor-dependent therapy into a diverse ecosystem of biological and technological solutions. Patients will receive organs from genetically engineered pigs, bioprinting labs, or even their own regenerated cells, while many others may avoid transplantation altogether through regenerative medicine, gene editing, and artificial organ implants. Advances in AI-driven allocation, precision medicine, and opt-out donation policies will expand access and efficiency, though disparities may persist between rich and poor regions. As bioengineered and artificial organs blur the boundaries between human, animal, and machine, the ethical, psychological, and cultural dimensions of identity, equity, and mortality will become central. Ultimately, the future of end-stage organ disease lies not only in replacing organs but in redefining what it means to heal, live, and thrive beyond biological limits.