Type I interferons (IFNs) are a family of potent cytokines with diverse functional effects on immunity. We explored this diversity against cancer and found expression of individual IFN subtypes within the tumour microenvironment (TME) results in a spectrum of outcomes. Eighty percent of mice inoculated with IFNa9-expressing B16 melanoma cells resulted in complete tumour clearance. Conversely, IFNa4-expressing tumours had delayed progression, but all mice succumbed to disease. We utilised bulk and single cell RNA sequencing to extrapolate the differences between these distinct phenotypes and validated these findings with flow cytometry. Bulk RNAseq profiling demonstrated that all tumours expressing IFN had a general proinflammatory phenotype with high immune infiltration. Interestingly IFNa4-expressing tumours displayed an ‘overheated’ phenotype which were characterised by a strongly Th1-polarised TME with increased ILC1s, NK cells and pro-inflammatory monocytes. In contrast, IFNa9-expressing tumours, which were eliminated, displayed a balanced cellular profile, including macrophages, ILC2s and fibroblasts. Whilst IFNa9- and IFNa4-expressing tumours had similar numbers of CD8+ T cells, the imbalance of signals led to functionally impaired CD8+ T cells that were ultimately inadequate to eliminate the tumour. We hypothesise that successful anti-tumour immune responses require a finely tuned balance of pro- and anti-inflammatory signals to prevent tumours from overheating. We are validating this finding by using cellular engineering techniques to manipulate the balance of pro- and anti-inflammatory signals in the TME to ‘cool-down’ overheated tumours and maximise the longevity of the anti-tumour immune response. We anticipate this knowledge will uncover novel immunotherapeutic targets and synergise with current immunotherapy.