<p>Thermoelectric materials (TE) have shown significant potential for power generation and localized refrigeration due to their ability to convert heat into electricity. Ca₉Zn_4+<i>x</i>Sb₉ is a promising TE material with low lattice thermal conductivity attributed to its complex structure and interstitial atom vacancies. However, understanding the impact of Zn vacancies in interstitial position on thermoelectric efficiencies remains a challenge. In this study, we conducted a systematic investigation of the thermoelectric properties of Ag-doped Ca₉Zn_{4.5−<i>x</i>}Ag_<i>x</i>Sb₉ (<i>x</i> = 0.05, 0.1, 0.15, 0.2) for the first time. Our findings reveal that increasing the occupancy rate of interstitial atoms significantly enhances electronic transport properties, thereby improving conductivity. It verifies that Ag doping pushes the Fermi level toward the valence band, indicating the metal behavior with the increase doping ratio. Through manipulation of phonon-electron decoupling, we achieved a peak <i>zT</i> value of ~ 0.63 at 873&#xa0;K for Ca₉Zn_4.45Ag_0.05Sb₉, which is close to twice of undoped Ca₉Zn_4.5Sb₉ with a maximum <i>zT</i> of about 0.37. These results not only experimentally demonstrate the promising efficiency of Ca₉Zn_4.45Ag_0.05Sb₉ but also offer a general and alternative strategy for tuning the thermoelectric properties of Zntil-phase materials through vacancy engineering.</p>