Abstract Summary Mass spectrometry is an increasingly important tool for the global interrogation of diverse biomolecules. Unfortunately, the complexity of downstream data analysis is a major challenge for the routine use of these data by investigators from broader training backgrounds. Omics Notebook is an open-source framework for exploratory analysis, reporting and integrating multiomic data that are automated, reproducible and customizable. Built-in functions allow the processing of proteomic data from MaxQuant and metabolomic data from XCMS, along with other omics data in standardized input formats as specified in the documentation. In addition, the use of containerization manages R package installation requirements and is tailored for shared high-performance computing or cloud environments. Availability and implementation Omics Notebook is implemented in Python and R and is available for download from https://github.com/cnsb-boston/Omics_Notebook with additional documentation under a GNU GPLv3 license. Supplementary information Supplementary data are available at Bioinformatics Advances online.