Enthalpic interaction between the elements determines the stability of the local structures in the alloy system. Multicomponent synergistic effect is expected to improve the thermal stability and the relevant properties by regulating the enthalpic interaction. In this work, the composition of Cu-Ni-Sn alloys is explained by introducing the cluster-plus-glue-atom mode, and the strong and weak enthalpic interaction elements Si and Zn, respectively, are chosen for multi-componentization of Cu-Ni-Sn alloys. The results demonstrate that the synergistic effect of Zn and Si improves the stability of both the Cu matrix and D022 or L12-γ′ phase, inhibits the discontinuous precipitation effectively and gains a notable higher strength-over-resistivity ratio (HR / ρR) than the Cu-15Ni-8Sn (wt. %) (C72900) alloy. After adding Si and Zn, the reinforcing enthalpic interaction between the elements is the crucial factor for the stability enhancement of the alloys, and it is embodied by two aspects: (a) the reducing elastic strain energy in the solution treated alloys; (b) the more homogeneous surface potential and the higher work function in the age treated alloys. Additionally, Compared with the Cu80Ni15Sn5 alloy that based on the ideal cluster formula, the Cu79.68Ni15.63Sn4.69 alloy, based on the modified cluster formula: {[Cu-CuxNi12-x]Cu3}a{[Sn-NiyCu12-y]Sn3}16-a, possesses a preferable thermal stability whatever solution treated or age treated state, and exhibits a decreasing amount of discontinuous precipitation although has a slightly lower HR / ρR, which is beneficial to the improvement of the workability of the alloys. The modified cluster formula is more suitable for the compositional design of Cu-Ni-Sn alloys. The work provides an effective theoretical and experimental basis for the composition design of high stability Cu-Ni-Sn alloys.