In lead-cooled fast reactors of the fourth generation, the high density and kinetic energy of lead–bismuth fluid can easily induce vibrations in slender, wire-wrapped fuel rods, leading to wear, fatigue, instability, or even failure, thereby posing a threat to reactor operational safety. To gain an in-depth understanding of the refined flow-field excitation and flow-induced vibration response of wire-wrapped fuel assemblies in lead–bismuth flow, this study established a strong fluid–structure interaction numerical analysis method based on computational fluid dynamics (CFD) and a multiphysics coupling platform. The method's accuracy was validated against experimental data. Modal analysis was then used to investigate the effects of wire-wrapping structural parameters on modal frequencies. Building on this, the study examined the influence of wire diameter and pitch on the flow field characteristics and structural vibration behavior of the rod bundle. The results indicate that increasing the wire diameter or decreasing the pitch significantly alters the velocity distribution within the rod bundle's flow field, resulting in greater pressure drops. Conversely, decreasing the wire diameter or pitch intensifies fuel rod vibration, as evidenced by increased amplitude and dominant vibration frequencies. Reducing the pitch leads to more isotropic vibration patterns, with vibration trajectories approximating a circular shape. The numerical analysis method proposed in this study provides an effective tool for researching the flow-induced vibration of wire-wrapped fuel assemblies in lead–bismuth reactors and offers valuable insights for optimizing wire-wrap structural design.