Based on the in-depth analysis of features of the process industry, the state of art of its operation control, and the global development of intelligent manufacturing, a new mode of intelligent manufacturing for the process industry, i.e., smart and optimal manufacturing, is proposed. After analysis of the development situation of the existing three-tier architecture (consisting of enterprise resource planning, manufacturing execution system, and process control system) and the control and management informatization system adopted by process enterprises, a smart and optimal manufacturing framework and prospects for future process enterprises are presented, followed by the analysis of key generic technologies that are critical for the successful deployment of intelligent manufacturing in the process industry. The fundamental challenges and open scientific problems to be addressed jointly by the communities of automation, computer and communication, and data science are also presented. Moreover, suggestions on the future development and deployment of smart and optimal manufacturing in the process industry are offered, include emphasizing the strategic position of the process industry, actualizing the strategic planning and top-level design.