Natural gases generally consist of mainly 12C and about 1.1％ of 13C. It is well known that a stable carbon isotope, 13C, has been widely used for the applications of medical, pharmaceutical, and agricultural tracers. As a result, the development of the separation and concentrating technology of 13C can cause of high value-added products and the possibility of the generation of new carbon materials. In general, there are two kinds of approaches to obtain a stable 13C isotope by the separation of cryogenic distillation. One is to obtain a concentrated 13CH4 isotope from natural gas. Another approach is to get concentrated 13CO by distillation followed by a chemical reaction of CH4 and H2O. In this study, rigorous process simulations of the cryogenic distillation have been performed and analyzed for the concentrated separation of 13C isotopes from LNG and NG by using commercial process simulator. Due to the very small differences of relative volatilities and separabilities of 12C and 13C, the process design and operation of effective separation and concentration of 13C need special strategies and feasibility studies. Utilization of vapor pressure data to acentric factor in SRK equation of state and optimized process conditions have been able to predict for the effective of the separation yield and concentration of 13C for the cryogenic distillation. The various operation strategies for both batch and continuous cryogenic distillation are also studied and suggested for the basic design of the process. Development of this study can provide a tool for the effective design and operation of the cryogenic separation of 13C.