The article introduces an updated version of the PharmMapper web server, a tool for identifying potential drug targets through reverse pharmacophore matching. The new version features a significantly expanded pharmacophore database, now containing 23,236 proteins with 16,159 druggable pharmacophore models and 51,431 ligandable pharmacophore models. This expansion covers 450 indications and 4,800 molecular functions, compared to the previous version's 110 indications and 349 molecular functions. The server also includes an improved user interface and a statistically meaningful ranking system for identified targets, enhancing the accuracy and reliability of the predictions. The updated PharmMapper is freely available at http://ilab.ecust.edu.cn/pharmmapper/ and is designed to support polypharmacology research by identifying multi-target drugs that can perturb disease-associated networks.The article introduces an updated version of the PharmMapper web server, a tool for identifying potential drug targets through reverse pharmacophore matching. The new version features a significantly expanded pharmacophore database, now containing 23,236 proteins with 16,159 druggable pharmacophore models and 51,431 ligandable pharmacophore models. This expansion covers 450 indications and 4,800 molecular functions, compared to the previous version's 110 indications and 349 molecular functions. The server also includes an improved user interface and a statistically meaningful ranking system for identified targets, enhancing the accuracy and reliability of the predictions. The updated PharmMapper is freely available at http://ilab.ecust.edu.cn/pharmmapper/ and is designed to support polypharmacology research by identifying multi-target drugs that can perturb disease-associated networks.