Sn-9Zn solder is a promising Pb-free solder, but it tends to form bulky intermetallic compounds (IMC) grains at the interface when soldered with common simple metal Cu or Ni substrates. Interfacial reaction between Sn-9Zn solder and Ni(Cu) solid solution substrates at 250 °C and 350 °C were systematically probed in this study. Results showed that when soldered at 250 °C, a Ni5Zn21 layer is formed at Sn-Zn/Ni-20Cu and Sn-Zn/Ni-40Cu joints; and Ni2Sn2Zn + Cu5Zn8 and Cu5Zn8 phases are formed in Sn-Zn/Ni-60Cu and Sn-Zn/Ni-80Cu joints, respectively. Fine-grained IMCs formed at the interface are formed even when the soldered time is prolonged to 16 h. This result indicates that Ni(Cu) solid solution substrates inhibit the rapid growth of IMC at the Sn-Zn/Ni-Cu interface. Ni(Cu) solid solution substrate can also provide various combinations of reaction products at the Sn-Zn/Ni-Cu joints. The Ni5Zn21 transfers to Ni2Sn2Zn + Cu5Zn8 phases when the Cu content increased to 60%, and a bi-layered structure Ni2Sn2Zn + Cu5Zn8 IMCs was formed in Sn-Zn/Ni(Cu) joints at 350 °C regardless of the Cu content in Ni(Cu) substrate (20–80%). These results would provide an effective support in designing Sn-Zn soldering system with optimized IMC layer to improve mechanical performance.