Sub-nanometer　noble　metal　catalysts,　especially　single　atom　(SA),　are　a　new　class　of　catalytic　materials　for　boosting　catalysis　and　possess　unique　catalytic　properties　and　high　atomic　utilization　efficiency.　Exploring　the　interaction　between　two　neighboring　atom　monomers　has　great　potential　to　further　improve　the　performance　of　SA　catalysts　and　deepen　the　understanding　on　the　catalytic　mechanism　of　heterogeneous　catalysis　at　the　atomic　level.　Herein,　we　demonstrate　that　the　synergetic　effect　between　neighboring　Pt　and　Ru　monomers　supported　on　N　vacancy-rich　g-C3N4　promotes　the　catalytic　CO　oxidation.　The　experimental　observation　and　theoretical　simulation　reveal　that　the　N　vacancy　in　the　g-C3N4　structure　builds　an　optimized　triangular　sub-nanometer　cavity　for　stabilizing　the　neighboring　PtRu　monomers　by　forming　Pt-C　and　Ru-N　bonds.　The　mechanistic　studies　based　on　the　in　situ　IR　spectrum　and　theoretical　simulation　confirm　that　the　neighboring　Pt-Ru　monomers　possess　a　higher　performance　for　optimizing　O2　activation　than　Ru-Ru/Pt-Pt　monomers　or　isolated　Ru/Pt　atoms　by　balancing　the　energy　evolution　of　reaction　steps　in　the　catalytic　CO　oxidation.　The　discovery　of　the　synergetic　effect　between　neighboring　monomers　may　create　a　new　path　for　manipulating　the　catalytic　properties　of　SA　catalysts.