Interactions in the tumour microenvironment (TME) are complex and pose a major oncological challenge. Immunotherapy has led to significant progress in recent years, however, not all patients benefit from this. An increasing number of trials try to modulate the TME. Interferon type I (IFN-I) proteins play an important role in the immune response, having many beneficial effects in patients with cancer, particularly when administered locally. This review finds that targeted intratumoural delivery of IFN-I to the TME may mediate optimal therapeutic effects in solid cancers, having extensive implications for clinical oncology. However, an increased understanding of the mechanisms is imperative to develop new and better treatments for solid cancers.