Dietary intake and nutritional status is an important environmental factor which can modulate metabolic-inflammation. In recent years, research has made significant advances in terms of understanding the impact of dietary components on metabolic-inflammation, within the context of obesity, type-2 diabetes (T2D) and CVD risk. Our work demonstrated that different fatty acids differentially modulate metabolic-inflammation, initially focusing on Nod-like receptor family, pyrin domain-containing three protein (NLRP3) inflammasome mediated IL-1β biology and insulin signalling. However, the paradigm is more complex, wherein data from the immunology field clearly show that nature of cellular energy metabolism is a key determinant of inflammation. Whilst metabolic-inflammation is a critical biological interaction, there is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation. The complex paradigm will be discussed within the context of if/how dietary components, in particular fatty acids, may modulate obesity, T2D and CVD risk, via inflammatory and metabolic processes.