Escherichia coli is increasingly employed for chemical production, with its industrial competitiveness now depending on both the expansion of its molecular repertoire through first-in-class pathways and achieving best-in-class titer, rate, and yield (TRY). Recent milestones include the first demonstration of producing aromatic homopolyester and poly(ester amide)s from glucose using engineered E. coli. To optimally maximize TRY, systems metabolic engineering leverages diverse tools such as genome-scale CRISPRi/sRNA libraries, dynamic biosensors, and redox-balancing modules to optimally channel cellular resources toward product formation. In parallel, in silico tools support retrobiosynthetic pathway design, flux optimization, and enzyme engineering. By integrating first-in-class pathway construction with best-in-class TRY optimization, E. coli is poised to drive the next generation of sustainable, large-scale biomanufacturing. Overall, this review outlines representative achievements, strategic approaches, and emerging prospects, highlighting how recent advancements are positioning E. coli as a versatile and competitive chassis for sustainable production of value-added chemicals and materials.