It is becoming increasingly clear that the tumour microenvironment (TME) adopts a changing and increasingly complex landscape as tumours evolve. Central to the TME, and alongside malignant cells, are tissue resident and recruited macrophages, other immune cells, and endothelial cells, with the latter critical for angiogenesis and tumour development. Tumour vessels provide oxygen and nutrients and are portals for immune cells. Tumour cells, immune cells and endothelial cells engage in multi-directional crosstalk that untimately influence tumour progression and treatment responses. Adding to complexity, the TME often consists of oxygenated, and oxygen deprived or hypoxic regions, with the latter significantly contributing to disease progression and treatment resistance. However, the function of immune cells and endothelial cells change with ageing, and this underexplored area likely influences the aged TME and disease outcomes in the elderly. Solid cancers such as mesothelioma with known carcinogen exposure (asbestos) take decades to reach a diagnosable size, often emerging in people aged 60 years or more. Here, we discuss the influence of ageing on the function of tumour-associated immune cells, focussing on macrophages, and their possible interactions with endothelial cells, and how this might impact the evolving mesothelioma TME in elderly people.