Abstract: Fibroblast growth factors (FGFs) and their receptors, fibroblast growth factor receptors (FGFRs), constitute an essential signaling system that is widely involved in development, tissue homeostasis, and metabolic regulation. In recent years, advances in cryo-electron microscopy and protein engineering have shifted FGF-FGFR research from the traditional receptor activation paradigm toward a new framework centered on protein-protein interactions and receptor conformation-mediated signaling bias. This review summarizes the structural basis of FGF-FGFR protein interactions, with particular emphasis on the asymmetric dimer model, the distinct receptor recognition mechanisms of paracrine and endocrine FGFs, and recent progress in the receptor dimerization threshold model. It further discusses the molecular mechanisms underlying FGFR signaling bias and summarizes recent progress in the design of engineered FGF analogs and FGFR agonists, aiming to provide new theoretical insights for precision therapies for metabolic diseases.