As the application of lithium-ion batteries (LIBs) expands beyond conventional electric vehicles (EVs) to heavy vehicles such as electric trucks or trams, the importance of thermal management in LIB systems is increasing, even at the module or pack level. In particular, because monitoring the thermal behaviors of each cell is not feasible, thermo-electrochemical modeling and simulations in the module or pack level are essential for analyzing and ensuring thermal stability. However, because the conventional lumped thermo-electrochemical models cannot reflect the actual structure of LIB cells, there might be considerable differences may exist between simulation and experimental results. To fill these gaps, we have newly developed a 3D microstructure-based digital twin model of a battery module (8.8 Ah/18.5 V, five LIB pouch cells in series) for an unmanned railway vehicle. Unlike traditional lumped models, our digital twin model accurately well reflects the internal structure of cells and can calculate the heat generation of each component inside a cell. As a result, contrary to a lumped model, the digital twin model can not only simulate the inhomogeneous temperature gradient inside a cell, but also estimates higher local maximum temperatures (TDT, max/TL, max = 137.2 °C/123.9 °C @ 10C discharge) in cells which can trigger thermal runaway. Therefore, microstructure-based digital twin modeling can alleviate concerns regarding the thermal runaway of LIB cells, modules, and packs, and provide safe operating conditions.