The integrity and composition of the tumour microenvironment (TME) is highly plastic, undergoing constant remodelling in response to instructive signals derived from alterations in the availability and nature of systemic host factors. This 'systemic milieu' is directly modulated by host exposure to modifiable lifestyle factors such as exercise. Host exposure to regular exercise markedly reduces the risk of the primary development of several cancers and might improve clinical outcomes following a diagnosis of a primary disease. However, the molecular mechanisms that underpin the apparent antitumour effects of exercise are poorly understood. In this Opinion article, we explore the putative effects of exercise in reprogramming the interaction between the host and the TME. Specifically, we speculate on the possible effects of exercise on reprogramming 'distant' tissue microenvironments (those not directly involved in the exercise response) by analysing how alterations in the systemic milieu might modulate key TME components to influence cancer hallmarks.