Immunotherapy has revolutionized cancer treatment, but predicting patient response remains challenging. Here, we presented Intelligent Predicting Response to cancer Immunotherapy through Systematic Modeling (iPRISM), a novel network-based model that integrates multiple data types to predict immunotherapy outcomes. It incorporates gene expression, biological functional network, tumor microenvironment characteristics, immune-related pathways, and clinical data to provide a comprehensive view of factors influencing immunotherapy efficacy. By identifying key genetic and immunological factors, it provides an insight for more personalized treatment strategies and combination therapies to overcome resistance mechanisms.