We demonstrated the use of combinatorial methods to optimize the filling of spent nuclear fuel (SNF) in metal canisters for final deep SNF repository, according to the maximal allowed thermal power per canister Pmax and the limit of n = 4 spent-fuel assemblies per canister. As a next step, the deposition time can be optimized by minimizing the required number of canisters M and the interim storage time. The method has been tested in detail for a typical pressurized water reactor (PWR), nuclear power plant (NPP) Krsko, SNF for different numbers of reactor cycles and different Pmax. The results show that the time interval between the last reactor cycle and the optimal deposition time varies between 3 and 30 yr for a typical PWR. The most significant contribution to the uncertainty of the calculated SNF decay heat (thermal power) is due to inaccurate cross sections taken from generic cross-section libraries. The quality of the results was verified by comparing the calculated M to the theoretical lower boundary Mmin. The idea behind the optimization method is universal and thus can be implemented for any SNF, canister, and repository design.