Smart manufacturing will transform the oil refining and petrochemical sector into a connected, information-driven environment. Using real-time and high-value support systems, smart manufacturing enables a coordinated and performance-oriented manufacturing enterprise that responds quickly to customer demands and minimizes energy and material usage, while radically improving sustainability, productivity, innovation, and economic competitiveness. In this paper, several examples of the application of so-called “smart manufacturing” for the petrochemical sector are demonstrated, such as the fault detection of a catalytic cracking unit driven by big data, advanced optimization for the planning and scheduling of oil refinery sites, and more. Key scientific factors and challenges for the further smart manufacturing of chemical and petrochemical processes are identified.