This volume constitutes the post proceedings of the 15th International Conference on Large-Scale Scientific Computations, LSSC 2025, which took place in Sozopol, Bulgaria, in June 16?20 2025. The 58 full papers included in thisbook were carefully reviewed and selected from 69 submissions. They were organized in topical sections as follows:Invited Papers; Numerical Methods: Analysis and Computations; Variational Analysis and Optimal Control; Space-Time Methods for PDE-Based Simulation and Optimization; Fractional Operators and Multi-Physics; Recent Advances in Computational and Applied Poromechanics; Mathematics and Algorithms for Predictive Digital Twins; Adaptive and Robust Domain Decomposition Methods; Applications of Metaheuristics to Large-Scale Problems; Large-Scale Models: from Life Sciences to Climate Research; HPCand HPDA: Algorithms and Applications; Numerical Solvers and Preconditioners for Differen tial Equations; Porous Media Flow and Transport; Fractional Differential Problems: Theoretical Aspects, Algorithms and Applications; and Contributed Papers.