The comprehensive antibiotic resistance of pathogens signifies the oneset of the "post-antibiotic era", and the myriad treatment challenges posed by "superbugs" have emerged as the primary threat to human health. Recent studies indicate that bacterial resistance and tolerance development are mediated at the metabolic level by various signaling networks (e.g., quorum sensing systems, second messenger systems, and two-component systems), resulting in metabolic rearrangements and alterations in bacterial community behavior. This review focuses on current research, highlighting the intrinsic link between signaling and metabolic networks in bacterial resistance and tolerance.