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With the continuous development of chemical industrial in high efficient, low-carbon and green, the chemical engineering has been gradually dragged to the development road on multi-scale, multi-disciplinary integration, which has been providing a variety of ideas and solutions for the problems of high efficient operation, energy saving and emission reduction encountered in process engineering. The chemical production process that includes a lot of physical and chemical processes in changing raw materials to final product is a multi-level, multifunctional complex process system, in which the material, energy and information flows are strongly coupling with each other. In this paper, the challenges of operation optimization for this complex system are deeply analyzed from the three levels of process control, unit optimization and system integration optimization, based on which the three scientific issues are then presented. They are the relationship between the process mechanism of complex material transformation and the system behavior characteristics, the relationship between the flow structure of the multi-processes with complex energy/mass coupling and the system efficiency, and the relationship between the intelligent regulation and control for the system behavior and the integrated optimization mechanism. To deeply understand and clearly answer the scientific issues, the material transformation mechanism, the system behavior, the flow structure and process parameters and their influences on material and energy consumptions as well as the waste emissions in chemical processes are detailedly investigated, based on which the integrated optimization theory and key technology for the high efficient use of the material and energy in chemical process are proposed to optimize and control the chemical processes and operations in industrial practice. Finally, the future research emphasis and the outlook of intelligent manufacturing in chemical process are presented.