Cooling water systems (CWSs) are extensively utilized in various industries to eliminate the excess heat and converse energy. Studies on CWSs mainly concentrated on finding the optimal cooler network structure. In addition, some works also considered the optimal design under varied operation conditions. However, in these works, once the optimal design of the cooler's network is determined, its arrangement remains fixed and cannot be adapted to accommodate diverse operating conditions. In this work, a flexible topology network concept is proposed to make the adjustment of network structure possible under different operation conditions. The CWS with integrated air cooler and flexible topology network has better overall performance, represented by a mixed integer nonlinear programming (MINLP) model that require advanced tools such as GAMS software. Case studies revealed that the proposed methodology can realize better energy-saving performance, and improve the economic performance under varied operation conditions. The impact of critical flexible nodes on system configuration and economy is achieved by sensitivity analysis.