As a large integrated energy system, district cooling system (DCS) is widely proposed for its favorable comprehensive performance. However, due to the high complexity of DCS structure and comprehensive influential variables on cooling demand, to propose an effective operational strategy that not only enhances energy efficiency but also ensures indoor thermal comfort is quite challenging. This research proposes a novel and online multi-objective optimization strategy for DCS operations, which minimizes both energy consumption and thermal discomfort, to tackle the aforementioned challenge. The proposed strategy incorporates accurate spatiotemporal cooling demand modeling: (1) On the one hand, cooling load models of both cooling dissipations during transport networks and cooling end consumers considering comprehensive influence of outdoor meteorological parameters are described; (2) On the other hand, all power consumption components in the DCS including chiller, pump, fan coil, fan of cooling tower, are built and connected with system cooling demand. Numerical experiments based on a real-world DCS are conducted to validate the proposed strategy. The results show that by adopting the proposed strategy, energy consumption cost and thermal comfort can be effectively optimized and can save an extra 5% of energy consumption comparing with published strategies.