The two-volume set, LNAI 16221 and 16222, constitutes the proceedings of the 4th Mexican International Conference on Artificial Intelligence, MICAI 2025, held in Guanajuato, Mexico, November 3, 2025 The 65 full papers presented in these proceedings were carefully reviewed and selected from 119 submissions. The papers presented in these two volumes are organized in the following topical sections: Part I - Machine Learning; Natural Language Processing and Neural Networks. Part II - Applications; Pattern Recognition; Computer Vision & Image Processing and Bioinformatics & Medical Applications.