District cooling systems have been widely used for their high economic and energy performance. However, insufficient consideration of chiller configuration selection and multi-cooling scenarios causes excessive equipment installed capacity and low energy efficiency. This paper proposes a collaborative optimization method and a compatible multi-objective optimization model to address the design and operation issues affecting the economic and energy benefits of district cooling systems. Firstly, the cooling period is divided into different cooling scenarios constructed by cooling load characteristics. Subsequently, the ε-constraint-Sequential Quadratic Programming method is used to solve the multi-objective optimization models under different chiller configurations and various cooling scenarios. Finally, the Analytic Hierarchy Process-Technique for Order Preference by Similarity to Ideal Solution method is used to get the installation scheme with optimal chiller configuration and the operation strategies under various cooling scenarios. The proposed method is applied to design and optimize a district cooling system with ice thermal storage. The optimal scheme is equipped with double-duty chillers (6 × 1800 RT, 1 × 500 RT) and water-cooled chillers (1 × 1800 RT, 1 × 900 RT), considering chiller configuration selection and multi-cooling scenarios. Compared with the conventional scheme using double-duty chillers (8 × 1800 RT) and water-cooled chillers (2 × 1800 RT), the annual costs and the annual electricity consumption are reduced by 11.03% and 11.78%, respectively. The results verify the effectiveness and advantages of the optimization method.