The performance of a micro-resonator highly depends on the rate of vibrational energy dissipation. Anchor loss is one of the major sources of energy dissipation in vacuum-encapsulated weakly coupled mode-localized sensors. To study anchor energy loss in weakly coupled-resonator systems, the Perfectly Matched Layer (PML) method is utilized to investigate the influence of key factors on the anchor loss quality factor of mass sensor, including the size and position of the coupled beam, the resonator dimensions, and the material properties of weakly coupled resonator. The results indicate that increasing the ratio of Young’s modulus between the substrate and resonator beam, enhancing the length-to-width ratio of the resonator beam, selecting appropriate coupling positions, and reducing the width of the coupled beam can effectively reduce anchor loss, thus improving the quality factor of mode-localized weakly coupled systems. Moreover, the anchor loss is not only related to the stress distribution at the anchor region but also closely related to the eigenfrequency of the coupled resonant system. These findings can provide valuable references for the design and optimization of mode-localized mass sensors.