Aluminum alloy A356 and pure magnesium bimetallic castings were produced by vacuum-assisted sand mold compound casting process. The effect of process parameters, i.e., pouring temperature, vacuum pressure, insert temperature and grit size of sandpaper, on impact strength of joint interface was investigated. The experiments were executed by using central composite design approach. Experimental data were utilized to formulate a second-order regression model. Scanning electron microscopy of joint interface revealed that a uniform joint interface consisting of three different layers is obtained due to the diffusion between A356 insert and Mg melt. X-ray diffraction and energy-dispersive X-ray spectroscopy patterns confirmed the formation of intermetallic compounds Mg2Al3, Mg17Al12 and Mg2Si at A356/Mg interface. The parameters were optimized by using desirability analysis (DA), response surface methodology and genetic algorithm (GA) techniques in order to maximize the impact strength. The maximum value of impact strength is obtained as 10.5, 10.68, 11.71 and 12.29 in experimental, regression, DA and GA, respectively. The best value of impact strength (12.29 MPa) is obtained by GA optimization at 661.13 °C pouring temperature, 200.02 mm of Hg vacuum pressure, 328 °C insert temperature and 1187.15 as grit size of sandpaper.