Eutectic In-48Sn was considered a promising candidate for low-temperature solder due to its low melting point and excellent mechanical properties. Both Cu2(In,Sn) and Cu(In,Sn)2formation were observed at the In-48Sn/Cu interface after 160 °C soldering. However, traditional mechanical polishing produces many defects at the In-48Sn/Cu interface, which may affect the accuracy of interfacial reaction investigations. In this study, cryogenic broad Ar+beam ion milling was used to investigate the interfacial reaction between In-48Sn and Cu during soldering. The phase Cu6(Sn,In)5was confirmed as the only intermetallic compound formed during 150 °C soldering, while Cu(In,Sn)2formation was proven to be caused by room-temperature aging after soldering. Both the Cu6(Sn,In)5and Cu(In,Sn)2phases were confirmed by EPMA quantitative analysis and TEM selected area electron diffraction. The microstructure evolution and growth mechanism of Cu6(Sn,In)5during soldering were proposed. In addition, the Young’s modulus and hardness of Cu6(Sn,In)5were determined to be 119.04 ± 3.94 GPa and 6.28 ± 0.13 GPa, respectively, suggesting that the doping of In in Cu6(Sn,In)5has almost no effect on Young’s modulus and hardness.