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. Due to the COVID-19 pandemic the conference was partially held online. The 19 revised full papers presented were carefully reviewed and selected from 38 submissions. The papers are organized in topical sections on mathematical programming; global optimization; stochastic optimization; optimal control; mathematical economics; optimization in data analysis; applications.