<p>This paper investigates the flow behavior and microstructural evolution of La-TZM alloy under high-temperature deformation conditions, and develops a physically based constitutive model. High-temperature tensile tests were conducted on the La-TZM alloy at 1000 °C and 1200 °C using a Gleeble thermal simulation testing machine. The microstructural evolution was systematically characterized by EBS, SEM, and TEM. The results indicate that the flow stress of the La-TZM alloy during high-temperature deformation is governed by La₂O₃ second-phase particles, dislocation motion, and dynamic recrystallization (DRX). However, existing constitutive models fail to accurately capture the complex flow behavior of this alloy. Therefore, a physically based constitutive model was established, incorporating the microscopic shear stress of forest dislocations, GND, thermally activated shear stress, and grain boundary effects. The model also considers the evolution of grain size, dislocation density, DRX, and void volume fraction. Material parameters were calibrated using a GA. The predicted values of yield stress, grain size, and flow stress exhibit good agreement with experimental data. Consequently, the proposed model can reliably describe the flow stress and microstructural evolution of La-TZM alloy during high-temperature deformation. This model provides theoretical guidance for the performance optimization of La-TZM alloy and the design of metal-forming processes.</p>