Abstract: The meso-structure of concrete was found to have a significant influence on its anti-penetration performance. However, the interfacial transition zone (ITZ) is extremely thin, making it difficult to be accurately characterized in numerical models. To address this issue, a three-phase meso-mechanical modeling method for concrete was proposed based on the secondary development of Abaqus using the Python language. Zero-thickness cohesive elements were inserted between the aggregates and the mortar matrix to simulate the ITZ, through which its mechanical behavior was characterized. Meanwhile, a user-defined material subroutine was developed, in which a pore equation of state, a strength surface, tensile/compressive damage evolution laws, and a strain rate effect were taken into consideration. The proposed meso-scale model was then combined with the material subroutine to simulate the penetration process of an ogive-nose steel projectile into a concrete target. The results indicate that the depth of penetration (DOP) is reduced by 18.0% when the aggregate volume fraction is increased from 0% to 40% under an impact velocity of 650 m/s. A reduction of 28.6% in DOP is observed when the aggregate strength is increased from 100 MPa to 200 MPa. Furthermore, a reduction of 17.1% in DOP is obtained when the relative strength ratio of the ITZ is increased from 20% to 100%. The regulatory effects of meso-parameters—namely the ITZ, aggregate content, and aggregate strength—on the anti-penetration performance are thus revealed. This study provides a theoretical basis for the meso-structural design of anti-penetration concrete.