Abstract: The accumulation of excessive internal pressure within the hermetic containment of α-decay radioisotope heater units (RHU) may cause cladding rupture and risk of radioactive material release. To address this safety issue, a fully-coupled model was developed which integrating radioactive decay, temperature attenuation, helium states, and cladding mechanical response. This model overcomes the limitation of conventional methods, which only consider the state change of helium. Taking light weight radioisotope heater unit (LWRHU) as an example, numerical simulations were performed to analyze cladding temperature and deformation under two typical scenarios: normal storage and accidental re-entry. The results show excellent agreement with RMSE and R² values of (0.06, 1.001 9) and (0.09, 0.986 8) for the two scenarios, confirming the model’s accuracy in predicting the RHU temperature decay. As decay progresses and helium accumulates, the slope of p-V curve increases significantly, which imparts a strong volume-sensitive characteristic to the internal pressure. Based on this, a p-V-t evolution equation for helium and a pressure-bearing p-V characteristic curve of the cladding were established. Two methods for determining the internal pressure are proposed: the graphical calibration method, which estimates internal pressure by matching helium and cladding curves in p-V space, though with some subjectivity in selecting the intersection point; and the self-consistent iterative method, which achieves a self-consistent solution by establishing a coupled isothermal p-V state between the helium and the cladding. This method is particularly suitable for high-temperature conditions where the cladding undergoes significant nonlinear deformation, and provides high accuracy in approximating the actual internal pressure. The proposed model and methods provide a theoretical basis and practical tools for the design optimization, safety assessment, and storage management of α-decay RHU systems. This method also facilitates the development of computational software for estimating the internal pressure in α-decay RHUs, thereby demonstrating substantial potential for practical engineering applications.