Tasmanian Devil facial tumour disease is an aggressive clonally transmissible cancer in Tasmanian devils. This is the core cause driving the decline in Tasmanian devil populations. There are currently no effective treatments for this disease and a better basic understanding of Devil facial tumour disease biology is needed. To this end, we build a custom whole-genome CRISPR-Knock out library suitable for interrogating Tasmanian Devil gene function. We then used this library to screen for essential genes in Devil facial tumour-derived cells. From this, we identified 168 genes (FDR<0.2) required for survival of Devil facial tumour cells, and we have now independently validated the top ranked essential genes. Through pathway analysis, we found an enrichment in cancer specific gene signatures within our gene hits, confirming the overall success of this strategy. Importantly, our data point to a potential therapy to kill Devil facial tumours, and we are investigating this possibility now. Overall, we describe the first use of whole genome CRISPR screening of the Tasmanian Devil genome, and these data may help us develop new ways to manage Devil facial tumour disease.