Laser ablation generated RhAl3O4+ heteronuclear metal oxide cluster cations have been mass-selected using a quadrupole mass filter and reacted with CH4 or CD4 in a linear ion trap reactor under thermal collision conditions. The reactions have been characterized by state-of-the-art mass spectrometry and quantum chemistry calculations. The RhAl3O4+ cluster can activate four C-H bonds of a methane molecule and convert methane to syngas, an important intermediate product in methane conversion to value-added chemicals. The Rh atom is the active site for activation of the C-H bonds of methane. The high electron-withdrawing capability of Rh atom is the driving force to promote the conversion of methane to syngas. The polarity of Rh oxidation state is changed from positive to negative after the reaction. This study has provided the first example of methane conversion to syngas by heteronuclear metal oxide clusters under thermal collision conditions. Furthermore, the molecular level origin has been revealed for the condensed-phase experimental observation that trace amounts of Rh can promote the participation of lattice oxygen of chemically very inert support (Al2O3) to oxidize methane to carbon monoxide.