The pursuit of high-power factor and low lattice thermal conductivity simultaneously in thermoelectric research is longstanding. Herein, great success has been achieved in SnTe-based materials by employing a proposed strategy of entropy engineering involving vacancies, thus leveraging the promising cocktail effect. Significant band convergence and flatness effects have given rise to exceptionally high density of state carrier effective mass and Seebeck coefficients. These effects have also led to the theoretical optimal carrier concentration closely aligning with the actual carrier concentration. Furthermore, the entropy engineering involving vacancies has induced pronounced lattice disorder and a wealth of nanostructures, facilitating multi-scale phonon scattering. Consequently, impressive thermoelectric performance is realized in AgSbPbGeSnTe: room-temperature ZT of ≈0.4, peak ZT of ≈1.3 at 623 K, and average ZT of ≈1.0 (300–773 K). A thermoelectric module, comprising this p-type material and the homemade n-type PbTe, is assembled, demonstrating a competitive conversion efficiency of 9.3% at a temperature difference of 478 K. This work not only provides valuable insights into the modulation of electron/phonon transports but also establishes an effective paradigm of entropy engineering involving vacancies.