The terms “Pico meter” and “technology” are combined to form “Picotechnology,” a term that is similar to Nanotechnology, which serves as the foundational cornerstone for Picotechnology. Similar to Nanotechnology, Picotechnology incorporates natural systems specifically cellular and subcellular processes as its reference standards. Picotechnology is defined as the manipulation of matter at atomic and sub-atomic level at a Picometer scale (10−12 meters) which represents the frontier beyond Nanoscale (10−9). Picotechnology in material science signifies to generate ultra-high-performance materials by specifically modifying atomic bonds, electronic structures, and so on. This chapter discusses the generation of materials with stability, reactivity, resilience that holds the capacity to revolutionize in various industries such as electronic, aerospace, biomedical science, and so on. Picotechnology in material science signifies to generate ultra-high performance materials by specifically modifying atomic bonds, electronic structures, and so on. Recent developments in picotechnology such as quantum control, high resolution spectroscopy, and medical imaging tools facilitate precise deception and examination of sub-atomic structures at Picometer scale are discussed. This article reviews the challenges involved in Picotechnology such as the development of instruments, theoretical modeling and reliability of systems. Research and Development (R&D) endeavors in Nanotechnology are largely responsible for the development of Picotechnology. Picotechnology current developments assume that the researchers eventually will be able to study the structure and system of Picometer scaling system. This review provides insights about principles, application, challenges, and future directions of Picotechnology in material science.