<p indent="0mm">Antimony sesquitelluride (Sb<sub>2</sub>Te<sub>3</sub>) is the most important hosting material for the development of high-performance phase-change memory and brain-like computing technology. This material has two crystalline phases, namely, the metastable cubic rock-salt structure with 1/6 atomic sites taken by randomly distributed vacancies, and the stable rhombohedral phase with layered structures and vacant gaps in hexagonal stacking. The former is an Anderson insulator (AI) and serves as the key ingredient for memory applications, while the latter is a prototypical topological insulator (TI). In this work, we propose a new heterophase homostructure concept for Sb<sub>2</sub>Te<sub>3</sub>, which in principle could utilize both the topologically protected surface state of the rhombohedral phase and the Anderson localization features of the cubic phase in the bulk interior to achieve ultralow-loss electron transport. To sustain the topological surface state, the edges of the device should be kept in rhombohedral phase with the thickness larger than <sc>~4 nm.</sc> The bulk interior of the sample should be transformed into cubic phase with strong electron localization. According to our density functional theory (DFT) results, the layered atomic building blocks for the two phases are quite similar, though their stacking sequence and degree of structural disorder are different. Thanks to the similar structure and mass density of the two phases, lattice mismatch is not expected to be present at the interface of the heterophase homostructure, superior to heterostructures made of different materials. To lend support to this heterophase homostructure concept, we have prepared a <sc>~500 nm</sc> thick rhombohedral Sb<sub>2</sub>Te<sub>3</sub> thin film on a silicon substrate via molecular beam epitaxy (MBE) and made an attempt to induce the phase transition in its bulk interior. A cross-sectional specimen for transmission electron microscopy (TEM) experiments was prepared by a dual beam focused ion beam (FIB) system. The TEM specimen along the electron beam direction was <sc>~80 nm.</sc> For standard TEM observation in short time, the damage brought by electron beam is very limited. However, when the electron beam was focused in an exposure area of <sc>~120 nm</sc> or below inside an electron microscope with a fixed accelerating voltage of <sc>200 keV,</sc> visible structural changes in the Sb<sub>2</sub>Te<sub>3</sub> specimen were observed. A gradual structural transition from the stable rhombohedral phase to the metastable cubic phase was observed under extensive electron beam irradiation over <sc>90 min.</sc> The<italic> in situ </italic>high-resolution TEM experiments revealed a clear vacancy disordering induced metastabilization process in the Sb<sub>2</sub>Te<sub>3</sub> specimen, where Sb atoms from the atomic stacks diffused into the vacant gap layers in Sb<sub>2</sub>Te<sub>3</sub> and eventually triggered a structural change from rhombohedral to cubic Sb<sub>2</sub>Te<sub>3</sub>. Our DFT calculations corroborated this picture, which showed a systematic increase in total energy as the vacant gap was gradually filled in rhombohedral Sb<sub>2</sub>Te<sub>3</sub>. The bonding environment of the Sb atoms in the gap for the two phases is entirely different. For the cubic phase, the Sb atoms in the gap are located as the center of octahedral structures with the bond angle of ~90°, which is consistent with the Sb atoms in the original rhombohedral and cubic phase. In stark contrast, the Sb atoms in the gap layers of rhombohedral phase are in a distorted bonding environment with bond angles of both ~110° and ~90°, leading to a large energy penalty for the rhombohedral phase. When the concentration of vacancies in the target layers reached 50%–70%, a change in stacking sequence from rhombohedral to cubic stacking was triggered. The critical vacancy concentration was mainly affected by the degree of compressive strain perpendicular to the target layers. In summary, we have discussed the design concept of a Sb<sub>2</sub>Te<sub>3</sub> based heterophase homostructure and demonstrated that this structure could be free of lattice mismatch via <italic>in situ</italic> TEM experiments and DFT calculations. Finally, we provided some guidelines for practical synthesis of Sb<sub>2</sub>Te<sub>3</sub> heterophase homostructure samples to explore the interaction between topological physics and Anderson localization of electrons, and to fabricate potential electronic devices of ultra-low power consumption.