The capability to consistently manufacture structures with sub-5 nm features has greatly accelerated scientific advancements in nanoscience and nanotechnology. However, most current methods are serial processes that are time-consuming and impractical for large-scale manufacturing at the sub-5 nm level. The challenge of achieving scalable and reproducible production of sub-5 nm structures poses a significant hurdle for both fundamental research and commercial implementations. In this review, we explore some representative sub-5 nm fabrication strategies, focusing on approaches that facilitate scalable and reproducible manufacturing. We highlight the most promising techniques such as extreme ultraviolet lithography, electron beam lithography, directed self-assembly and atomic layer lithography that hold potential breakthroughs in both research and industry, based on criteria such as resolution, scalability, reproducibility and their applicability in photonics such as surface-enhanced spectroscopies, terahertz science, and nonlinear optics, as well as in electronics such as quantum devices, molecular devices and memory devices. The evolution of scalable and reproducible sub-5 nm manufacturing methods will ultimately revolutionize next-generation devices, encompassing quantum technologies, neuromorphic computing chips, and the mass production of integrated circuits.