This book constitutes refereed proceedings of the 21st International Conference on Mathematical Optimization Theory and Operations Research, MOTOR 2022, held in Petrozavodsk, Russia, in July 2022. The 21 full papers and 3 short papers presented in this volume were carefully reviewed and selected from a total of 88 submissions. The papers in the volume are organised according to the following topical headings: invited talks; integer programming and combinatorial optimization; mathematical programming; game theory and optimal control; operational research applications.