As an important civil and military infrastructure, airport runway pavement is faced with threats from cluster munitions, since it is vulnerable to projectile impacts with internal explosions. Aiming at the damage assessment of an island airport runway pavement under impact, this work dealt with discrete modeling of rigid projectile penetration into concrete pavement and the calcareous sand subgrade multi-layer structure. First, the Discrete Element Method (DEM) is introduced to model concrete and calcareous sand granular material features, like cohesive fracture and strain hardening due to compression, with mesoscale constitutive laws governing the normal and shear interactions between adjacent particles. Second, the subsequent DEM simulations of uniaxial and triaxial compression were performed to calibrate the DEM parameters for pavement concrete, as well as subgrade calcareous sand. Prior to the multi-layer structure investigations, penetration into sole concrete or calcareous sand is validated in terms of projectile deceleration and depth of penetration (DOP) with relative error ≤ 5.6% providing a reliable numerical tool for deep penetration damage assessments. Third, projectile penetration into the airport runway structure with concrete pavement and calcareous sand subgrade was evaluated with validated DEM model. Penetration numerical simulations with various projectile weight, pavement concrete thickness as well as striking velocity, were performed to achieve the DOP. Moreover, the back-propagation (BP) neural network proxy model was constructed to predict the airport runway penetration data with good agreement realizing rapid and robust DOP forecasting. Finally, the genetic algorithm was coupled with the proxy model to realize intelligent optimization of pavement penetration, whereby the critical velocity projectile just perforates concrete pavement indicating the severest subsequent munition explosion damage.