Abstract: Structural materials of nuclear reactors and nuclear chemical equipment have been in a service environment where high temperature and radiation are coupled with each other for a long time, and the material hardness shows significant temperature dependence. The prediction of radiation hardening is an important means to establish the relationship between microscopic defect evolution and macroscopic mechanical property degradation, which is of great significance to the improvement of material radiation resistance and engineering applications. In this work, a material hardness prediction model that can uniformly describe the indentation size effect (ISE), radiation damage gradient and temperature effect was constructed based on the plastic zone volume weighting framework. By establishing a response function that is dually dependent on temperature and irradiation dose, the gradient distribution of irradiation defects and thermal evolution dynamics are simultaneously introduced into the constitutive equation, and a basic framework for multi-physics coupling modeling is constructed, which can effectively characterize the base material, thermal microstructure, ISE, and the respective hardening contributions of irradiation defect. Based on the idea of decoupling, a multi-physics model parameter calibration method is proposed, which can use limited experimental data to achieve continuous prediction of unmeasured working conditions, making up for the shortcomings of traditional discrete fitting methods. Systematic verification was conducted using typical zirconium alloys and nickel-based alloys as model materials. The results show that the model can reproduce the hardness-depth response of materials at different temperatures (298-673 K) and irradiation doses with high accuracy. At the same time, by accurately describing the peak non-monotonic evolution characteristics of the response function m(T), it reveals the hardening mechanism dominated by the competition between defect coarsening and thermal recovery at medium temperatures. This work provides a theoretical tool that is both physical and robust for understanding and predicting the radiation hardening behavior of materials under multi-physics coupling.