Electrochemical　CO2　reduction　reaction　(ECO2RR)　offers　an　opportunity　to　sustainably　convert　CO2　into　value-added　fuels　and　chemicals　by　using　the　electricity　that　could　be　generated　by　renewable　energies.　Recently,　enormous　efforts　are　focused　on　the　development　of　metal-based　catalysts　for　the　selective　ECO2RR　with　high　efficiency.　Multi-metallic　catalyst　design　emerges　as　one　of　the　most　promising　strategies　for　the　promotion　of　the　Faradaic　efficiency　(FE),　the　current　density,　and　the　lowering　of　the　overpotential　of　the　catalysts　for　ECO2RR.　The　synergistic　effects　of　the　different　metal　sites　in　the　hybrid　catalysts　are　of　significance　for　the　enhancement　of　the　ECO2RR　performance.　This　review　summarizes　the　rational　design　of　multi-metallic　catalysts,　including　alloy,　atomically　dispersed　multi-metallic　sites,　and　others,　along　with　the　popular　metal　elements　studied　in　multi-metallic　catalysts　to　clarify　the　advantages　of　different　metal　elements　for　ECO2RR.　The　density　functional　theory　(DFT)　simulations　and　advanced　in-situ　characterizations　that　contribute　to　demystifying　the　synergies　between　metal　elements　are　highlighted.　Challenges　and　outlook　concerning　the　catalyst　design　and　reaction　mechanism　of　multi-metallic　catalysts　for　ECO2RR　are　also　discussed.　©　2021　Elsevier　Ltd