The further application exploration of TZM alloys have been hindered by the limited strength especially at high temperatures. Herein, we propose a strategy to enhance the mechanical properties of TZM alloys by introducing heterostructures through Y2O3 doping combined with rotary forging (RF). The particle stimulated nucleation (PSN) mechanism promotes fine grains (FGs) nucleate close to the micron-sized second phase particles. The mechanical properties of Y2O3-TZM (YTZM) alloy are improved through the synergistic strengthening influence of back stress strengthening and second phase strengthening. The ultimate tensile strength (UTS) of YTZM at room temperature and 1000 °C is 820 MPa and 433 MPa, respectively, which are about 15% and 51% higher than that of TZM. In addition, the FCC-oxides generated by adding Y2O3 can trigger twinning, stacking faults, and 9R structures during high-temperature deformation, and the long-period stacked ordered phase (LPSO) nucleates at the stacking faults and twin boundaries through the 9R structures, which is more conducive to alleviate the stress concentration at the oxide/matrix interface and improve the dislocation blocking ability. The present strategy provides a paradigm for the development of high-performance TZM alloys through creating heterostructures.