Natural gas hydrate deposits in marine sediments represent a vast potential energy resource, yet their commercial extraction remains a complex scientific and engineering challenge due to the intricate thermo-hydro-mechanical-chemical coupling processes triggered during production. This perspective paper synthesizes recent progress and outlines persistent hurdles in understanding the coupled mechanical-seepage-thermal response inherent to gas hydrate exploitation, while introducing a novel theoretical and methodological framework that integrates cross-scale constitutive modeling, multiscale permeability upscaling, and nonlinear flow characterization to better interpret key feedback mechanisms. Looking forward, overcoming these barriers requires interdisciplinary approaches leveraging advanced sensing technologies, machine learning-assisted modeling, and novel upscaling methodologies. Furthermore, internationally collaborative long-term field trials with comprehensive monitoring are essential to validate next-generation simulators and develop adaptive management strategies.