For decades, Moore’s Law has delivered the ability to integrate an exponentially increasing number of devices in the same silicon area at a roughly constant cost. This has enabled tremendous levels of integration, where the capabilities of computer systems that previously occupied entire rooms can now fit on a single integrated circuit. Although traditional scaling has slowed over the past decade, we have made tremendous progress as an industry with new approaches including chiplet-based architectures, domain-specific accelerators, and advanced packaging technologies which have enabled major milestones including the first exascale supercomputers. As we look into the future, we need to accelerate the pace of innovation to drive the next decade of advancement in high-performance computing. By far, the largest limiting factor to delivering continued compounded growth in computation power is energy efficiency. In this paper, we highlight a holistic strategy for accelerating innovation in energy efficiency required for next-generation high-performance computing and ultimately achieving zettascale performance.