To explore the degree of constraint by Global Navigation Satellite System (GNSS) and Interferometric Synthetic Aperture Radar (InSAR) data on the Maduo earthquake within a layered earth model structure and to gain an insight into the seismogenic mechanism and the seismic risk in the surrounding area, this study employs D-InSAR technology to acquire the InSAR co-seismic deformation field of the Maduo earthquake on 22 May 2021. Utilizing both GNSS and InSAR data, the inversions constrained by single and joint data are conducted and compared to determine the co-seismic slip model and fault plane stress distribution of the Maduo earthquake. Additionally, this paper calculates the Coulomb stress changes induced by 14 M ≥ 7 strong earthquakes, considering co-seismic effects, post-seismic viscoelastic relaxation, and inter-seismic tectonic stress loading, on 19 fault segments within the Bayan Har block research area (96°E~106°E, 29°N~36°N) since 1900. The findings are as follows: (1) The maximum line-of-sight (LOS) deformation was approximately 0.9 m. The joint inversion rupture was primarily located in the Dongcao Along Lake section (~98.6°E), aligning with previous research outcomes. (2) The cumulative Coulomb stress at the Maduo earthquake’s source location was −0.1333 MPa, while the inter-seismic stress loading amounted to 0.0745 MPa. The East Kunlun Fault, Maduo–Gande Fault, Ganzi–Yushu Fault, and Dari Fault C exhibited considerable stress loading, warranting attention due to heightened seismic risk. (3) Based on three different co-seismic slip models, the stress disturbance results caused by the Maduo earthquake to the surrounding area and fault did not differ significantly. After the earthquake, the seismogenic fault still has high seismic risk.