This book constitutes the proceedings of the 21st International Conference on the Integration of Constraint Programming, Artificial Intelligence, and Operations Research, CPAIOR 2024, held in Uppsala, Sweden, during May 28-31, 2024. The 33 full papers and the 9 short papers presented in the proceedings were carefully reviewed and selected from a total of 104 submissions. The content of the papers focus on new techniques or applications in the area and foster the integration of techniques from different fields dealing with large and complex problems. .