In an era of genomics-guided precision medicine there is an increasing need for models that reflect the hallmarks of cancer and the molecular diversity of patient tumours. New cell culturing methods are transforming our ability to derive cell models from healthy and diseased tissues, with increased success rates, and linked to patient genomic and clinical data. I will update on our efforts as part of the Human Cancer Models Initiative (HCMI) to create a new biobank of molecularly-annotated tumour organoids as a community resource. Furthermore, I will present how we are beginning to use these organoid cultures for chemical and genetic screen to identify new molecular targets and biomarkers of therapy response. These early studies are laying the foundation for a next-generation tumour organoid functional genomics platform to help guide the development of future precision cancer medicines.