Transition metal substituted polyoxometalates (TMS-POM) provide a redox-active metal center, (Fe, Ru, Mn or else), with a totally inorganic ligand system, featuring rigid polydentate binding sites, high electron-acceptor character, extreme robustness and interesting structural and coordination properties, in some cases, mimicking the coordination geometry of natural oxygenase enzymes. Their synthesis and reactivity can be promoted by microwave (MW) induced dielectric heating. In particular, MW irradiation induces a very efficient and selective hydrothermal synthesis of the diamagnetic, air-stable [RuII(DMSO)PW11O39]5−. Its catalytic activity has been screened with shunt oxidants like NaIO4 and KHSO5 and PyCl2NO. Under dioxygen and MW irradiation, [RuII(DMSO)PW11O39]5− catalyzes the oxidation of DMSO to DMSO2 in water. FeIII-POMs with nuclearities 1–4, namely [α-Fe(H2O)SiW11O39]5− (FeSiW11), [γ-Fe2(H2O)2SiW10O38]6− (Fe2SiW10), [α-Fe3(H2O)3SiW9O37]7− (Fe3SiW9) and [β-Fe4(H2O)10(XW9O33)2]n− (Fe4X2W18, X = SeIV, TeIV; AsIII, SbIII; n = 4, 6) were also found to catalyze the MW assisted cyclohexane oxygenation with high turnover frequencies. Preliminary results indicate that the Krebs-type Fe polyoxotungstates can also promote the oxidative cleavage of 3,5-ditert-butylcatechol with molecular oxygen.