Ever-growing performance of supercomputers nowadays brings demanding requirements of energy efficiency and resilience, due to rapidly expanding size and duration in use of the large-scale computing systems. Many application/architecture-dependent parameters that determine energy efficiency and resilience individually have causal effects with each other, which directly affect the trade-offs among performance, energy efficiency and resilience at scale. To enable high-efficiency management for large-scale High-Performance Computing (HPC) systems nowadays, quantitatively understanding the entangled effects among performance, energy efficiency, and resilience is thus required. While previous work focuses on exploring energy-saving and resilience-enhancing opportunities separately, little has been done to theoretically and empirically investigate the interplay between energy efficiency and resilience at scale. In this article, by extending the Amdahl’s Law and the Karp-Flatt Metric, taking resilience into consideration, we quantitatively model the integrated energy efficiency in terms of performance per Watt and showcase the trade-offs among typical HPC parameters, such as number of cores, frequency/voltage, and failure rates. Experimental results for a wide spectrum of HPC benchmarks on two HPC systems show that the proposed models are accurate in extrapolating resilience-aware performance and energy efficiency, and capable of capturing the interplay among various energy-saving and resilience factors. Moreover, the models can help find the optimal HPC configuration for the highest integrated energy efficiency, in the presence of failures and applied resilience techniques.