Abstract It is of significant importance to evaluate energy consumption and to optimize configuration of energy utilization in process systems. A comprehensive approach based on material flow analysis (MFA) and exergy flow analysis (EFA) is proposed to evaluate energy consumption and integrate energy utilization of a process system, in which energy-consuming devices and exothermic devices exist simultaneously. By using the proposed approach, the energy consumption of streams in the process system is evaluated by energy consumption distribution, and the energy efficiency of the system is improved by both the improvement of local sub-systems and the integration of energy utilization of the entire system. A natural gas purification plant with a processing capacity of 200 × 104 m3/d is taken as the case study to demonstrate the detailed implementation of the proposed approach. Results show that the streams with high energy consumption intensity are indicators of energy-intensive sub-systems, and energy conservation of these sub-systems can dramatically reduce the energy consumption of the system. In this case study, after the process improvement, the energy consumption of the desulfurization sub-system reduces by 9.62%, and the energy consumption of the exhaust gas treatment sub-system reduces by 21.02%. Furthermore, after the integration of heat exchange network of the entire system, the energy consumption of the system reduces by 2.16 × 105 kW. By these from the part to the whole strategies, the total energy-saving can reach 1.07 × 106 kW in the system. The proposed approach can be used for effectively identifying the bottlenecks of the energy consumption and improving the energy utilization of process systems.