SIRIUS 4 is a highly advanced computational tool designed to rapidly identify metabolites from tandem mass spectra. It integrates high-resolution isotope pattern analysis and fragmentation trees to provide a comprehensive assessment of molecular structures from MS/MS data. The tool offers significant improvements in identification accuracy and speed compared to previous versions, achieving over 70% identification rates on challenging metabolomics datasets. SIRIUS 4 includes a web service, CSI:FingerID, which predicts molecular fingerprints without requiring a molecular structure database, making it suitable for analyzing novel or hypothetical compounds. The tool also supports negative ion mode data and integrates additional training data and molecular properties to enhance its performance. The graphical user interface allows for intuitive analysis, and the software is open-source, available under the GNU General Public License (Version 3). SIRIUS 4 has been validated through various evaluations and biological case studies, demonstrating its effectiveness in identifying unknown compounds and providing valuable insights into metabolic pathways and biological processes.SIRIUS 4 is a highly advanced computational tool designed to rapidly identify metabolites from tandem mass spectra. It integrates high-resolution isotope pattern analysis and fragmentation trees to provide a comprehensive assessment of molecular structures from MS/MS data. The tool offers significant improvements in identification accuracy and speed compared to previous versions, achieving over 70% identification rates on challenging metabolomics datasets. SIRIUS 4 includes a web service, CSI:FingerID, which predicts molecular fingerprints without requiring a molecular structure database, making it suitable for analyzing novel or hypothetical compounds. The tool also supports negative ion mode data and integrates additional training data and molecular properties to enhance its performance. The graphical user interface allows for intuitive analysis, and the software is open-source, available under the GNU General Public License (Version 3). SIRIUS 4 has been validated through various evaluations and biological case studies, demonstrating its effectiveness in identifying unknown compounds and providing valuable insights into metabolic pathways and biological processes.