Fish underpin future nutritional security, supplying high quality protein, iron, iodine and vitamin A that are critical to childhood development and deficient in many staple foods. In 2018, 54.1 million tonnes of fish were produced by farming, generating US$138.5 billion and employing 19.3 million people directly, mostly in developing nations. With expansion and intensification, disease losses are increasing and are a priority for the FAO sub-committee on aquaculture. In most developing countries, disease mitigation comprises over-stocking to compensate, and use of readily available antibiotics. Indeed 67 different antimicrobials are used in the 11 major producing countries, contributing to the global pool of antimicrobial resistance (AMR). Accurate identification of the causes and sources of infectious disease is essential for implementation of evidence-based treatment, biosecurity and prevention. Pathogen genomics can provide sufficiently detailed information but has, to date, been too expensive and time consuming. Lab-in-a-backpack uses nanopore sequencing technology and low cost, low waste sample preparation to generate whole pathogen genome sequence data from diagnostic samples on the farm without laboratory support. Our simplified, safe, workflow includes a cloud-based identification tool that returns near real-time information about the pathogen using any laptop or smartphone. This enables evidence-based treatment, epidemiological tracing, AMR surveillance and the production of simple low-cost, locally produced “autogenous” vaccines to protect the next crop. These big-data-informed but locally implemented solutions, align well with FAOs recently proposed Progressive Management Pathway for Improving Aquaculture Biosecurity and can deliver real advances in local economy, nutritional security, antimicrobial stewardship and animal welfare.