Understanding the meso-structure evolution and macro-mechanical property changes in rocks under thermo-hydro-mechanical (THM) treatment is crucial for advancing and managing deep geological projects. However, due to complex discontinuity networks in rocks, achieving an accurate characterization that quantitatively correlates the micro-macro mechanical behaviors under THM conditions remains challenging. This study introduces a groundbreaking multi-scale analysis method called the grain interface-based discrete element model (GIB-DEM) to tackle this issue. By utilizing digital imaging processing (DIP) and meso-mechanical measurements, the GIB-DEM directly determines the meso-mechanical parameters of bonds, eliminating the need for complex calibration found in traditional methods. After validating the GIB-DEM through experimental and numerical Brazilian Splitting tests, we investigate the macro- mechanical behaviors of rock under different THM conditions. Our results indicate that the increase in the tensile strength at 75 °C is attributed to the tensile strength increase of quartz grain interfaces. The development of micro-cracks on the interfaces of feldspar and feldspar-quartz accounts for the decrease in tensile strength of rock under thermal and hydraulic treatment. Overall, this pioneering research provides valuable insights for optimizing Enhanced Geothermal System (EGS) projects and effectively managing Hot Dry Rock (HDR) resources.