ABSTRACT Overview: Genetics and genomics technologies are essential tools for cancer research and help to improve care for cancer patients. The Genomics Shared Resource (GSR) provides University of Colorado Cancer Center (UCCC) members high-quality and cost-effective services and technical support for high-throughput genomic investigation to study cancer pathogenesis, therapeutics, genetic susceptibility, and biomarker development, and develop strategies for targeted and personalized medicine. Services and Expertise: GSR offers methodologies for quantitative assessment of DNA/RNA including evaluation of human and murine cells harboring shRNA and CRISPR libraries that UCCC members obtain from the Functional Genomics Shared Resource (FGSR). GSR provides genome-wide analyses of DNA sequence, transcriptomes, epigenetics and cytogenomics using next generation sequencing (NGS) and gene microarrays; and single cell genomic and transcriptomic analyses including single cell immune profiling and spatial gene expression. Equipment: GSR houses equipment to support DNA next-generation sequencing (NGS) (Illumina NovaSeq 6000 and Illumina MiSeq); single-cell genomics (10X Genomics Chromium; Mission Bio Tapestri; Fluidigm C1 and Biomark HD Systems); DNA microarray analysis (Affymetrix GeneChip systems; Illumina iScan system; and Agilent SureScan Microarray system) and Affymetrix, Agilent and Illumina microarray and sequencing software. Management: GSR is an institutional core managed by the UCCC, and is overseen by H Ford, Associate Director for Basic Research. Use of Services: Since July 2016, GSR has provided services to 432 investigators. Twenty-nine percent of users (125) were UCCC members, representing all four programs and resulting in 118 peer reviewed publications, 18% with an IF ≥ 10. Operating Budget: CCSG funding represents 2% of the annual operating budget of $4.4M. The remaining support is from user fees (98% $4.3M). Innovation and Developments: The GSR team supports UCCC members with commercial genomic tools including single cell genomics for cancer research. GSR develops and optimizes customized methods for specific cancer research applications. Consultation and Education: GSR provides consultation for designing and analyzing reliable genomics experiments in conjunction with the Biostatistics and Bioinformatics SR (BBSR) and helps members stay updated with the advancement of technology through seminars and hands-on training. Future Directions: GSR has four main future directions that are in high demand by UCCC investigators: 1) optimize 10X Genomics Visium spatial gene expression solution and methods for single cell genomics; 2) adopt Olink proteomics with NGS readouts; 3) adopt Nanopore single molecule sequencing; and 4) enhance NGS capability by continuously upgrading our technologies.