We propose a general mathematical model for various process integration problems, involving mass integration, heat integration, simultaneous mass and heat integration, and property integration. The process units, including regenerators/interceptors, mixers, and splitters are represented using blocks. The blocks are arranged in a two-dimensional grid, and the arrangement of these blocks gives rise to various process integration networks. The existence of connecting streams between adjacent blocks and jump flows among all blocks enables the necessary interaction between different blocks via material and energy flows. The size of the block superstructure is determined by the number of layers with mixing operations, process units, product streams, and heat integration stages. The general process integration model is formulated as a mixed-integer nonlinear optimization (MINLP) problem with the minimization of total annual cost as the objective. We demonstrate our approach using four case studies from the process integration literature.