The intricate relationship between the mechanical properties of concrete and its internal microstructure underscores the importance of comprehending explosion performance and damage mechanisms at a mesoscopic level to effectively enhance blast resistance. This study employed three-dimensional (3D) mesoscale models to numerically investigate the dynamic behavior of concrete mixed with coarse aggregates under contact explosion. Rigorous validation of numerical models and simulation techniques was untaken through the contact explosion tests. The study explored mesoscopic damage mechanisms in heterogeneous concrete targets with randomly distributed coarse aggregates, drawing comparisons with a homogeneous concrete target. Critical mesoscopic parameters influencing the contact explosion resistance of concrete were thoroughly examined. Structural effects of coarse aggregates emerge as pivotal, shifting the damage mode from overall failure with spalling-dominated damage in homogeneous concrete to localized failure in mesoscopic concrete. The mesoscopic concrete experienced a distinct four-stage damage evolution—cratering, crack initiation, perforation, and dynamic fragmentation—diverging from homogeneous concrete with multi-layer spalling originating from the boundaries. The exponential attenuation of shock waves observed in homogeneous concrete was locally disrupted by coarse aggregates in mesoscopic concrete, attributed to wave impedance mismatch and aggregate extrusion effects. Mortar strength primarily contributed to concrete cracking, with minimal impact on damage modes. Failure modes were predominantly influenced by the content and particle size of coarse aggregates. Higher volumetric fractions significantly reduced concrete spalling, while increased coarse aggregate size exacerbated perforation failure. This comprehensive study advances our understanding of blast-resistant concrete design at a mesoscopic level, providing valuable insights for strategies aimed at enhancing structural resilience.