The paper describes methodological approaches of applying the thermodynamic analysis to assess the efficiency of complex chemical and engineering systems, as well as to identify the scientifically-based areas for improving the energy sector. Modern chemical and engineering systems including the hydrocarbon processing plants are characterized by the high specific energy intensity and complex engineering topology. The sophistication of such facilities can be objectively assessed based on the exergy analysis. The exergy analysis makes it possible to carry out a quantitative and qualitative assessment of any type of energy at the enterprise. Moreover, it provides an opportunity to adequately evaluate the potential of the energy utilization including secondary energy resources, combustible hydrocarbon gases, industrial wastes, and effluents. The paper presents methodological approaches to determine the exergy types and calculate the exergy balance, considering the specifics of hydrocarbon processing plants. The exergy balance of the study subject represented in the form of a Grassmann diagram has been calculated using the above provisions. Besides, the exergy of all types of fuel consumed has also been calculated, as well as the industrial processes consuming the largest amount of the fuel exergy for functioning have been determined. Finally, according to the data presented, the main directions for improving the efficiency of the hydrocarbon processing plants have been proposed.