This monograph highlights pertinent problems in nuclear fuel optimization. It shows that the current approach does not allow us to predict the synergic effects leading to fuel-related accidents, and is characterized by great uncertainty with regards to estimating fuel cladding failure conditions and the reduced efficiency of fuel operation. The book describes in detail a new philosophy of nuclear fuel optimization based on the synergic paradigm, applicable to both operating and prospective reactors, in order to minimize radioactive leakage under normal and emergency fuel operating conditions, to resolve the safety-efficiency contradiction for nuclear fuel operation, and to predict new synergic effects due to processes of self-organization in the reactor core. It will appeal to researchers, academics, PhD students and engineers engaged in developing prospective nuclear reactor designs, as well as those who verify the safety and efficiency of nuclear fuel operation under increasingly challenging core conditions.