The sustained increase in energy density in lithium-ion battery modules requires robust thermal management strategies to mitigate excessive heat accumulation. In this study, a directional thermal decoupling strategy is systematically evaluated in an 8S2P module comprising 60 Ah pouch cells by implementing a three-dimensional coupled electrochemical–thermal conjugate framework. Under continuous 2C discharge at an elevated ambient temperature, five inter-cell insulation sheets and five lateral thermal interface materials coupled to serpentine cold plates are comparatively evaluated. Nanoporous aerogel-like barriers limit heat conduction along the stacking direction but significantly hinder lateral diffusion toward the module edges, raising the maximum temperature to between 332.5 and 333.7 K and the temperature difference to 13.5 K, while yielding lower heat rejection rates ranging from 169.8 to 171.7 W. Conversely, anisotropic graphite sheets enhance in-plane heat spreading, reduce maximum volumetric heat generation, decrease maximum temperature to 322.3K, and raise Q˙rej to 187.0W. At the lateral interface, a conformable AlN/PDMS composite minimizes conductive resistance, yielding an optimal heat rejection rate of 188.94 W and maintaining maximum temperature at 321.97K. These findings establish quantitative design criteria to effectively balance inter-cell thermal isolation with active heat evacuation under severe nominal operating regimes.