Micro thermoelectric generator (μ-TEG) attracts more and more attention due to its small size and high power density. Many two-dimensional thermoelectric materials with high performance have facilitated the development of μ-TEG. However, the performance of μ-TEG fabricated by these great thermoelectric materials is significantly degraded due to size effect, interfacial effects (include contact effect and boundary effect) and structure effect. To accurately assess the performance degradation degree from material to μ-TEG and guide the device fabrication, an experiment-verified mathematical model considering interfacial and size effects is proposed. Firstly, the phonon/electron temperature distribution in thermoelectric leg of μ-TEG is analyzed to investigate the device-level thermoelectric properties of material. Then based on the device-level thermoelectric properties, the actual power generation performance model of μ-TEG is established to conduct the influence analysis of these effects (boundary, size, contact and structure effects) on material and device. Finally, the thermoelectric leg thickness (Hte) is optimized to realize optimal power generation. The study results reveal that boundary and size effects weaken the device-level thermoelectric properties, and the reduction trend is more obvious when Hte is smaller, especially when Hte ≤ 20 μm. The decrease from the material intrinsic figure of merit ((ZT)m) to the device figure of merit ((ZT)D) is owing to the boundary effect, structure effect and contact effect, and the dominant factor of this decrease changes from structure effect (Hte<7 μm)to contact effect (Hte ≥ 7 μm) as Hte increases, which points to a main optimization direction for (ZT)D for different Hte. As for contact effect, the electrical contact resistivity (re,c) has a more significant impact on weakening the performance of μ-TEG than thermal contact resistivity (rk,c), and their optimization goals are explored (re,c ≤ 5.1 × 10−12 Ω·m2, rk,c ≤ 9.3 × 10−8 K·m2/W). At given electrical and thermal contact resistivity, there exists an optimal Hte for achieving the optimal power generation (Popt) and a large range of Hte for achieving 95%Popt, and the optimal Hte increases with increasing electrical and thermal contact resistivity. This study can reduce the processing difficulty and save time and economic costs of μ-TEG fabrication, which can avoid the blind fabrication of μ-TEG.