Highly stable and long-life power supply systems are crucial to the success of space exploration missions. The systematic analysis of the service lives and stability of radioisotope thermophotovoltaic (RTPV) generators with general purpose heat sources (GPHSs) is the cornerstone of future practical space applications. Its operational lifetime is mainly limited by the degradation caused by the irradiation of key transducer components by the isotope source, while its operational stability is mainly related to the temperature variation of the external environment. The irradiation and temperature stability as the main influencing factors of GPHS-RTPV were studied. Results indicate that the output performance of the GPHS–RTPV was maintained at 50.15% after 1 × 1013 n/cm2 neutron and 927.84 Gy γ irradiation. The service life was conservatively estimated to be 19.883 years according to equivalent irradiation experimental results. In addition, the output performance of the GPHS–RTPV fluctuates linearly with temperature, the gradient of Pmax with temperature was −6.7 μW/K·cm2 in a range of 276.5–354.5 K, and higher output at low temperatures. This study explored the lifetime and service stability of GPHS-RTPV under actual operating conditions in space, and lays the foundation for future practical applications.