In response to the modern combat requirements for “low collateral damage and high-precision pinpoint strikes” against large-scale reinforced concrete structures, an integrated numerical simulation framework for the “penetration-detonation ” process of LGBs (laser-guided bombs) was proposed and validated, utilizing the Euler-Lagrange coupling algorithm and restart technology. The framework, implemented on the LS-DYNA finite element platform, enabled dynamic coupling of multiple physical fields. A full-scale, three-story reinforced concrete building was used as the target, and two typical combat scenarios were defined to systematically simulate the temporal response and peak overload during projectile multi-layer penetration, as well as the energy distribution characteristics of detonation products across floors and the pressure-time history curves. Furthermore, the influence of incident attitude and fuze delay on both local and overall building damage was quantitatively analyzed. The results demonstrate that both combat scenarios can effectively damage the target; however, significant differences are observed in the energy concentration and damage patterns: a top attack results in energy concentrated on the middle and lower floors, with localized high damage, whereas a lateral attack leads to a broader distribution of energy. The findings provide quantitative insights for target damage assessment, operational mission planning, and optimization of fuze timing parameters.