This book constitutes the refereed proceedings of the 12th International Conference on Optimization and Applications, OPTIMA 2021, held in Petrovac, Montenegro, in September-October 2021. The 22 full and 3 short papers presented were carefully reviewed and selected from 63 submissions. The papers are organized into the following topical sub-headings: mathematical programming, global optimization, discrete and combinatorial optimization, optimal control, optimization and data analysis, and game theory and mathematical economics.