Non-volatile memory (NVM) devices with non-volatility and low power consumption properties are important in the data storage field. The switching mechanism and packaging reliability issues in NVMs are of great research interest. The switching process in NVM devices accompanied by the evolution of microstructure and composition is fast and subtle. Transmission electron microscopy (TEM) with high spatial resolution and versatile external fields is widely used in analyzing the evolution of morphology, structures and chemical compositions at atomic scale. The various external stimuli, such as thermal, electrical, mechanical, optical and magnetic fields, provide a platform to probe and engineer NVM devices inside TEM in real-time. Such advanced technologies make it possible for an in situ and interactive manipulation of NVM devices without sacrificing the resolution. This technology facilitates the exploration of the intrinsic structure-switching mechanism of NVMs and the reliability issues in the memory package. In this review, the evolution of the functional layers in NVM devices characterized by the advanced in situ TEM technology is introduced, with intermetallic compounds forming and degradation process investigated. The principles and challenges of TEM technology on NVM device study are also discussed.