Over the last few years, protocols have been established to develop the “next generation” of cancer models, in vitro propagating cultures that can be verified to more closely represent the tumor from which they originated. Several groups have demonstrated that organoid cultures and conditionally reprogrammed cells in combination with unique media formulations offer new tools to address current gaps in our understanding of cancer initiation, development, and progression. Systematic application of these novel culture methods now present an opportunity to develop a large library of cancer models that can be made available as a community resource to investigators in academia and the biopharmaceutical industry. In response to the opportunity, the National Cancer Institute’s (NCI) Office of Cancer Genomics (OCG), in the Center for Cancer Genomics (CCG), together with international institutions, has established a consortium, the Human Cancer Models Initiative (HCMI). HCMI’s goal is to make available to the scientific community large numbers of “next generation” in vitro cancer models that are not encumbered with excessive intellectual property (IP) constraints. In addition to clinical annotation, the cancer models, the “parent” tumor, and a case-matched control sample need to have their genomes and transcriptomes characterized by sequencing. This will enrich the models greatly as it will allow researchers using them to establish correlations between the somatic and inherited genotypes of the tumors and their response to small molecules and other experimental utilizations. The characterization needs to be conducted using validated methods in a high-throughput fashion with a rapid turn-around time. The aim is to have all the characterizations conducted on biomolecules from the same biospecimens for optimal analytical integration for data comparability. This task order is to sequence the genomes and transcriptomes of each cancer model, the “parent” tumor and case-matched normal. Molecular characterization data will be made available through CCG’s Genomic Data Commons (GDC, https://gdc.nci.nih.gov/index.html). To promote model use by the community, the HCMI members have committed to establish a comprehensive online catalog in which all generated models will be listed, to be developed under this task order. This HCMI Catalog will collate model data from several sources and provide a web-based query tool to search for models of interest. The data collated in the catalog will include those key model variables deemed the most important features upon which investigators would make selection decisions. The data will include a range of tissue donor demographic and clinical diagnostic information, summaries of somatic genomic changes, and administrative information. The catalog will be searchable, and search results will be downloadable and include pointers out to primary data sources.