The growing demand for real-time monitoring and ultrasensitive sensors has driven the development of innovative smart materials and nanostructures for sensing applications. Among various cross-functional platforms, non-layered 2D (2-dimenstional) materials have emerged as an outstanding class of sensing materials due to its atomically thin nanostructures and tuneable functionalities. In this chapter, we explore the technical principles that underpin the synthesis and properties of non-layered 2D materials, while emphasising the design of components and sensing mechanisms governing various sensor technologies. The component design and sensing mechanism governing various sensor technologies are highlighted. An in-depth examination of the fundamental engineering strategies for non-layered 2D materials across various sensing applications is explicated, elucidating the structure-interaction-sensitivity correlations between the sensing materials and the analytes. Finally, we discuss the challenges associated with non-layered 2D materials for sensing applications and possible solutions.