Enhanced external counterpulsation (EECP) is widely utilized in rehabilitating patients after percutaneous coronary intervention (PCI) and has demonstrated efficacy in promoting cardiovascular function recovery. Although the precise mechanisms of the therapeutic effects remain elusive, it is widely postulated that the improvement of biomechanical environment induced by EECP plays a critical role. This study aimed to unravel the underlying mechanism through a numerical investigation of the in-stent biomechanical environment during EECP using an advanced multi-dimensional 0/1D-3D coupled model. Physiological data, including age, height, coronary angiography images, and blood velocity profiles of five different arteries, were clinically collected from eleven volunteers both at rest and during EECP. These data contributed the development of a patient-specific 0/1D model to predict the coronary volumetric flow and a 3D stented coronary artery model to capture the detailed in-stent biomechanical features. Specifically, an immersed solid method was introduced to address the numerical challenges of generating computational cells for the 3D model. Simulations revealed that EECP significantly improved the biomechanical environment within the stented arteries, as evidenced by increased time-averaged wall shear stress (resting vs. 20 kPa vs. 30 kPa:​ 1.39 ± 0.4773 Pa vs. 1.82 ± 0.6856 Pa vs. 1.96 ± 0.7592 Pa, p = 0.0009) and reduced relative residence time (resting vs. 20 kPa vs. 30 kPa:​ 1.06 ± 0.3926 Pa⁻¹ vs. 0.89 ± 0.3519 Pa⁻¹ vs. 0.87 ± 0.3764 Pa⁻¹, p < 0.0001). Correspondingly, low-WSS/high-RRT surfaces were obviously reduced under EECP. These findings provide deeper insights into EECP’s therapeutic mechanisms, thereby offering basis to optimize EECP protocols for enhanced clinical outcomes in post-PCI patients.