Metal matrix syntactic foams are playing an increasingly important role in different structures. Their application is primarily aimed at weight reduction and energy absorption. The present research uses sensitivity analysis, response surface methodology, and principal component analysis to quantify the effect of matrix yield strength, matrix-to-filler ratio, ceramic sphere wall strength, and wall thickness-to-diameter ratio on the critical compressive strength of metal matrix syntactic foam. It was found that the thickness-to-diameter ratio and strength of the sphere wall are the determining factors in the evolution of the compressive strength, but the matrix strength has less effect on the output.