ABSTRACT New transformative single-cell genomics technologies and spatial multiplex in situ methods provide an opportunity to interrogate the complexity of the dynamic tumor ecosystem at unprecedented resolution. Our project aims to make single cell genomics data, such as that from the Cancer Moonshot Initiative, more explorable and interpretable by the broader cancer research community. We propose to enhance UCSC Xena, a widely-used cancer genomics data visualization resource, with new, full-featured single cell data visualizations for investigator-specified, Moonshot-aligned use cases. We will employ User Centered Design (UCD), a research-backed process and methodology that involves iterative interactions with users and collaborators, throughout the development of these visualizations. We will work closely with two Cancer Moonshot projects, following UCD methodologies, to ensure our visualizations and interfaces serve research needs and are easy to use. In Aim 1 we will collaborate with two cancer research groups to develop novel visualizations for single cell Cancer Moonshot data. We will collaborate with UCSF-led NCI’s Drug Resistance and Sensitivity Network to enhance the Xena Browser to elucidate changes in tumors and surrounding microenvironment in response to therapy, including a visualization to leverage clinical outcomes from bulk tumor data. We will collaborate with OHSU Human Tumor Atlas Network (HTAN) center to develop multi-modal visualizations for the HTAN data, including a novel cross-mapping visualization for spatially resolved and non-spatial data multi-modal data. Aim 2 will develop the software infrastructure needed to support these accessible, high-performance single-cell data visualizations. This will include performance enhancements for the Xena Browser, hardening our integration with Jupyter Notebook/RStudio and adding connectors to single cell data analysis tools, and, finally, incorporating a UCSC-developed Cell State and Microenvironment signature library into our visualizations. Aim 3 will develop user training and support to promote adoption of new visualizations and connected analyses, disseminating these new visualizations and analyses to the widest possible community.