This book highlights new and original contributions on Graph Theory and Combinatorial Optimization both from the theoretical point of view and from applications in all fields. The book chapters describe models and methods based on graphs, structural properties, discrete optimization, network optimization, mixed-integer programming, heuristics, meta-heuristics, math-heuristics, and exact methods as well as applications. The book collects selected contributions from the CTW2020 international conference (18th Cologne-Twente Workshop on Graphs and Combinatorial Optimization), held online on September 14-16, 2020. The conference was organized by IASI-CNR with the contribution of University of Roma Tre, University Roma Tor Vergata, and CNRS-LIX and with the support of AIRO. It is addressed to researchers, PhD students, and practitioners in the fields of Graph Theory, Discrete Mathematics, Combinatorial Optimization, and Operations Research.