Abstract: Modern projectiles are usually designed to penetrate into the multi-layered slabs, i.e. multi-layered reinforced concrete (RC) structures, and to be fired on time at the predetermined positions, making efficient damage to specific personnel, facilities or building structures. Due to the initial oblique and attack angles in the process, the trajectory is prone to continuous deflection, affecting seriously the attack accuracy of projectiles. To predict the ballistic characteristics of typical warheads and to provide a concise recommendation for projectile penetration and protective design, a oblique penetration test was reproduced firstly on typical multi-layer concrete targets and RC targets to verify the reliability of the simulation approach for the analysis on trajectory, velocity, oblique and attack angles of projectiles. Secondly, the prototype projectiles and typical 8-layered RC structure were designed, and the penetration analysis was carried out under different initial oblique and attack angles (0°~30°, −3°~3°), nose shapes (sharp-, truncated- and double-ogival), length-to-diameter ratios (8~12) and centroid positions (front, middle and rear positions). The results show that the ballistic deflection is more severe at the initial positive attack angle than that at the negative attack angle, the warhead with truncated-ogival and double-ogival nose shapes can improve the stability of projectiles, the decrease of length-to-diameter ratio and the rear centroid position can make against the stability of projectiles. Based on the simulation results for typical warheads, a recommendation for projectile penetration and protective design of multi-story RC structures was proposed.