Methodological and technological innovations in high-throughput genomic and transcriptomic sequencing are critical to the GCID’s mission of deepening and broadening our understanding of infectious diseases. However, critical gaps remain in our ability to generate, analyze, and interpret high-throughput sequencing data for infectious disease research. Certain scientific questions cannot be addressed using existing ‘omics technologies and methods, and for other questions, the cost and throughput of generating and interpreting genomic and transcriptomic data severely limit the scale at which these technologies can be leveraged. Moreover, many genomic capabilities, and the data generated using them, are only accessible to a small subset of the scientific community in large, well-resourced research centers. Leveraging an unrivaled combination of interdisciplinary expertise, institutional resources, and technological infrastructures, the Technology and Data Core (TDC) will advance methodological innovation, optimization, and dissemination that closes these critical gaps and enables genomics-driven research at scale both within the GCID and across the wider infectious disease research community. The TDC will accomplish this through the following three Aims: 1) develop innovative and enabling methods and tools (we will devise and implement novel methodologies and tools that will render currently intractable questions in infectious disease accessible to genomics-driven research), 2) optimize and scale up existing protocols and tools (we will work to further improve and optimize cutting-edge methods and tools for sample processing and data generation), and 3) rapidly release and make accessible new data and methods generated by our Center (we will offer access to productionized laboratory services and containerized bioinformatic pipelines). In addition to closing key methodological and analytical gaps for the scientific community at large, these advances will enable cutting-edge research in all four GCID Projects, helping reveal key insights into the evolutionary paths, physiological adaptations, and cellular interactions that underlie the impacts of viruses, bacteria, fungi, parasites, and vectors on human health. Importantly, the TDC will also work closely with the Administrative Core to integrate sample and data tracking across the Center and to facilitate timely and comprehensive sharing of protocols, tools, resources, and data.