Supported single atoms constitute excellent models for understanding heterogenous catalysis and have achieved breakthroughs during the past years. How to prevent the aggregation and modulate activity of these species via metal-support interaction should be considered for practical applications. This work presents simple methods involving the creation of carbon- (on carbon nanotube (CNT)) or oxygen-vacancies (on TiO2) to stabilize nickel and ruthenium single atoms. The defective supports and the resulting catalysts are characterized by a large variety of techniques. These analyses show that this strategy is efficient for the preparation of ultra-dispersed catalysts. Comparison of the catalytic performances of these catalysts for the CO2 hydrogenation reaction is also reported. Catalysts supported on TiO2 are more active and sometimes more stable than those deposited on CNT. Nickel catalysts are very selective for the production of CO, and ruthenium catalysts are more selective for the production of methane. Most importantly, it is shown that, in the case of Ru, a direct correlation exists between the electronic density on the metal and the selectivity; electron-rich species produce selectively methane, while electron-deficient species orientate the selectivity toward CO. This work may figure a new way for the synthesis of ultra-dispersed catalysts for various applications.