B cells and T cells are important components of the adaptive immune system and mediate anti-cancer immunity. In this talk, I will present two recent studies that harness multi-omics technologies to unveil groundbreaking insights into immune cell immunosurveillance across metastatic sites and patient-specific responses to tumours. Our research reveals a dynamic co-evolution between B and T cell immune responses and metastatic cancer genomes, with B cell clones demonstrating remarkable predictability in immunosurveillance—a finding with broad relevance across immune-mediated diseases. Using single-cell multi-omics in pancreatic cancer, we identify two distinct immune microenvironments and their driving mechanisms: myeloid-enriched (linked to poor prognosis) and adaptive-enriched (associated with robust B/T cell clonal expansion and better outcomes). This work offers a novel blueprint for prioritising antibody sequences for therapeutic development and guiding rational combination immunotherapies, paving the way for more effective, personalised cancer treatments.