Worsening global warming, the demand for sustainable chemicals and foods, and the societal imperative to enable healthier and longer lives are redefining the mission of bioengineering. Over the next decade, systems metabolic engineering—where systems-level understanding guides metabolic design and is empowered by synthetic biology, rapid laboratory evolution, and AI—will become an essential approach for addressing these intertwined global challenges. A central challenge is the decarbonization of chemical and materials manufacturing.