<p>Nanoscale concentration modulation (NanoCM) is effective in tuning both functional and mechanical properties of shape memory alloys (SMAs) and high/medium entropy alloys (HEAs/MEAs), making NanoCM engineering recognized as a novel strategy to improve materials’ performance in practical applications in recent years. As a system applicable for developing both SMAs and MEAs, the quaternary Ti–Nb–Zr–Sn system is found to be able to generate NanoCM via spinodal decomposition (SD), which is an economic way of achieving NanoCM in bulk materials. However, the kinetic process of SD in the quaternary Ti–Nb–Zr–Sn system remains unclear at present because it is challenge for both experiments and molecular dynamics simulations to address multicomponent systems. In this work, we developed an SD model for the Ti–Nb–Zr–Sn system by integrating the phase-field model and the Calphad method and systematically studied the SD process of the Ti–Nb–Zr–Sn system. It is found that phase separation of Ti–Nb occurs during the SD process, with Sn residing in Nb-lean regions and Zr forming novel Zr-rich shells surrounding Nb-rich regions, which is in sharp contrast to conventional SD patterns. Moreover, Sn is found to be effective in widening the composition window for SD. The findings of this work will provide guidance for designing Ti–Nb–Zr–Sn-based SMAs, MEAs, and HEAs with desired mechanical and physical properties.</p>