Fabricating artificially tilted multilayer thermoelectric devices with high efficiency remains a key challenge. The material genome engineering method provides an effective approach to this challenge. Herein, the material genome databases are established in order to screen the matching materials (N) and geometrical parameters of N/Bi0.5Sb1.5Te3 artificially tilted multilayer thermoelectric devices based on high-throughput calculation. The transverse figure of merits of N/Bi0.5Sb1.5Te3 artificially tilted multilayer thermoelectric devices can be predicted with a performance indicator Gamma(N) = alpha(N)center dot(170-alpha(0.42)(N)) (alpha N and alpha N are Seebeck coefficient and electrical conductivity of N, respectively). The optimal matching materials YbAl3, Co, Ni and Bi are found through the indicator. YbAl3/Bi0.5Sb1.5Te3 artificially tilted multilayer thermoelectric device is fabricated with optimal geometrical parameters. The conversion efficiency reaches about 1.0%, increased by more than 3.3 times as compared with the highest data reported by other groups. Our work demonstrates that the high-performance artificially tilted multilayer thermoelectric devices can be rapidly designed and fabricated via material genome engineering method.