This book constitutes the post-conference proceedings of the 4th International Conference on Machine Learning, Optimization, and Data Science, LOD 2018, held in Volterra, Italy, in September 2018. The 46 full papers presented were carefully reviewed and selected from 126 submissions. The papers cover topics in the field of machine learning, artificial intelligence, reinforcement learning, computational optimization and data science presenting a substantial array of ideas, technologies, algorithms, methods and applications.