The LNCS 16416, constitutes the refereed post-conference proceedings of the 18th International Conference on Combinatorial Optimization and Applications, COCOA 2025, held in Tianjin, China, during November 28&30, 2025. The 44 full papers included in these volumes were carefully reviewed and selected from 113 submissions. The area of combinatorial optimization and its applications, including algorithm design, theoretical and experimental analysis, and applied research of general algorithmic interest.