In the past two decades, we have taken large strides towards understanding the role of the microbiota (the trillions of microorganisms inhabiting the human body) and the microbiome (their genes) in human health. Individual microbial or viral pathogens are implicated in the etiology of many cancers, including gastric, colon, and cervical cancer. Still more cancers likely arise from the interplay of many different microbial taxa, their metabolic activities, the host’s genotype and immune system activity, and factors such as host diet, current and former smoking status, and environmental exposures. We propose to advance cancer microbiome research through three specific aims. This work will be performed in the context of the popular QIIME 2 microbiome bioinformatics platform and the Qiita public microbiome data repository and pooled analysis system. In our first aim, we will improve access to cancer microbiome bioinformatics methods and data through the creation of a Galaxy interface for QIIME 2, improved support for working with QIIME 2 in the R programming language and Galaxy GUI ecosystem, popular for cancer research, the development of a resource for cancer microbiome pooled analysis, the development of a cancer- focused microbiome bioinformatics workshop series, and by making QIIME 2 and cancer microbiome data accessible from within the NCI Cloud Resources. Our second aim will develop a microbiome multi-omics bioinformatics platform driven by the needs of the cancer research community through creating QIIME 2 plugins for metabolomics, metatranscriptomics, metagenomics, and metaproteomics with developers working in these areas. Many important cancer microbiome projects have made advances by integrating these different data types, yet considerable technical hurdles remain to making microbiome multi-omics bioinformatics accessible by all researchers whose projects would benefit from these methods. To facilitate this, we will create a microbiome multi-omics bioinformatics developer conference, following the model of our recent Teaching and Developing QIIME 2 conference. Our third aim will improve the reproducibility of cancer microbiome bioinformatics methods, and the reliability of cancer microbiome bioinformatics results, by expanding several features related to tracking data provenance in QIIME 2, and helping users submit their microbiome multi-omics raw data to archival repositories. Much of this work will occur in collaboration with NCI Informatics Technology for Cancer Research (ITCR) and Cloud Resources project teams, several of whom we’re already beginning to collaborate with.