<p>Oxide thermoelectrics stand out for their low cost, rich raw materials and eco-friendliness, yet pristine In₂O₃ suffers from low intrinsic carrier density, high lattice thermal conductivity and unstable oxygen vacancies, severely hampering its thermoelectric performance. Herein, we fabricate Ho-doped In₂O₃ via solid-state reaction coupled with spark plasma sintering, and systematically clarify the doping effects and intrinsic mechanisms on crystal structure, electrical/thermal transport and mechanical behaviors. Characterizations verify that Ho³⁺ successfully substitutes for In³⁺ to form homogeneous substitutional solid solutions, accompanied by a gradual expansion of lattice parameters. Benefiting from Ho doping, the carrier concentration is boosted by 45-fold, and the electrical conductivity rises from 0.56 S· to 181 S·cm⁻¹. The optimal power factor of 5.8&#xa0;μW·cm⁻¹·K⁻¹ is achieved at 973&#xa0;K, 3.2 times that of pure In₂O₃. The large mass and ionic radius differences between Ho³⁺ and In³⁺ generate intense point-defect scattering, cutting lattice thermal conductivity by 62%. Notably, a distinctive decoupling effect of mechanical properties is observed: Young’s modulus declines from 76 to 43 GPa, while Vickers hardness continuously increases with doping level. The maximum ZT value reaches 0.31 at 973&#xa0;K for <i>x</i> = 0.0015, ~ 5.17 times as the undoped counterpart, and a broad performance optimization window exists within <i>x</i> = 0.0015–0.0021. Mechanism analysis reveals that Ho doping realizes the synergistic improvement of multi-performance via three pathways: lattice distortion and oxygen vacancy modulation, 5d/6&#xa0;s orbital hybridization, and enhanced point-defect scattering. This work not only clarifies the regulation mechanism of rare earth doping in In₂O₃ but also offers a novel strategy for developing high-performance rare earth-doped oxide thermoelectric materials.</p>