Styrenic block copolymers are widely used in HMPSA formulations, with tackifier resins and oil plasticizer. Although most commercial formulations are based on SIS, mixtures of SIS and SBS are also used to reduce cost. However, the use of SBS is restricted because it generally leads to decrease in tack. In this work, pure SIS and SBS and a SIS/SBS mixture were used in formulations with aliphatic, aromatic, aliphatic hydrogenated, and aliphatic-aromatic copolymer resins, at three different oil contents, according to a 3(3-1) factorial design. Interaction effects among the components were evaluated, showing a strong dependence of the HMPSA final properties on the combination of resin/rubber used. It was found that a blend of aliphatic and aromatic resins is the best tackifier for SIS, while for SBS the best choice is an aromatic-aliphatic copolymer. These results were explained in terms of specific compatibility, which was correlated to the polarizability of the material.