<p>The inherent crystal mechanical anisotropy of Cu₆Sn₅ can easily trigger abnormal grain growth and induce cracks in tin-copper solder joints, potentially causing early joint failure. Therefore, investigating the regulatory mechanisms of microalloying elements such as Mn and Zn with regard to mechanical anisotropy is crucial to improving the reliability of solder joints in service. The effects of doping with Mn and Zn on the crystal and electronic structure, as well as the mechanical properties, of the compound η′-Cu₆Sn₅ were systematically investigated using first-principles density functional theory. Relative formation-energy comparisons indicate that Mn substitution at the Cu4 site is energetically favored among the considered Mn-on-Cu configurations, while Zn substitution at the Sn3 site is favored among the considered Zn-on-Sn configurations. These results are interpreted as relative site-preference trends within dilute substitutional η′-Cu₆Sn₅ models, rather than as complete thermodynamic phase-stability predictions. Doping with Mn and Zn atoms decreases the mechanical anisotropy of η′-Cu₆Sn₅ and alters its mechanical properties. The mechanical anisotropy weakening is more obvious when co-doping at the Cu position. Moreover, most of the selected Mn/Zn-doped configurations improve the shear resistance of η′-Cu₆Sn₅, making it less prone to fracture. The findings of this research offer valuable theoretical insights into designing and optimizing the composition of high-reliability solders in the field of microelectronic packaging.</p>