This volume constitutes the refereed proceedings of the 4th International Conference on Optimization and Learning, OLA 2021, held in Catania, Italy, in June 2021. Due to the COVID-19 pandemic the conference was held online.

The 27 full papers were carefully reviewed and selected from 62 submissions. The papers presented in the volume are organized in topical sections on synergies between optimization and learning; learning for optimization; machine learning and deep learning; transportation and logistics; optimization; applications of learning and optimization methods.