Some Keggin-structural (hetero)polyoxotungstates with a lacunary hole, such as undecatungstosilicate ([SiW₁₁O₃₉]^8-, SiW₁₁), greatly sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactams. In this study, the effects of lacunary-substituted derivatives of SiW₁₁ were tested to determine if the lacunary hole is required for the sensitizing effect. Initially, it was supposed that the hole functioned as a binding site that interacts with some bacterial components. However, most of the lacunary-substituted species had stronger effects than SiW₁₁, indicating that the hole is not essential for the sensitizing effect. Undecatungsto(ferri)ferrosilicate ([SiW₁₁O₃₉Fe]^6/5-) was the most potent compound tested, but undecatungstocobaltosilicate ([SiW₁₁O₃₉Co]^6-) gave better results according to the fractional inhibitory concentration index. Small lipophilic cations enhanced the sensitizing effect, but bulky cations inhibited it. This suggests that a charge interaction between the tungsten compounds and some unknown materials in the culture medium or bacterial cells plays an important role in the sensitizing effect.