The onset and progression of cardiovascular diseases with the major underlying cause being atherosclerosis, occur during chronic inflammatory persistence in the vascular system, especially within the arterial wall. Such prolonged maladaptive inflammation is driven by macrophages and their key mediators are generally attributed to a disparity in lipid metabolism. Macrophages are the primary cells of innate immunity, endowed with expansive membrane domains involved in immune responses with their signalling systems. During atherosclerosis, the membrane domains and receptors control various active organisations of macrophages. Their scavenger/endocytic receptors regulate the trafficking of intracellular and extracellular cargo. Corresponding influence on lipid metabolism is mediated by their dynamic interaction with scavenger membrane receptors and their integrated mechanisms such as pinocytosis, phagocytosis, cholesterol export/import, etc. This interaction not only results in the functional differentiation of macrophages but also modifies their structural configurations. Here, we reviewed the association of macrophage membrane biomechanics and their scavenger receptor families with lipid metabolites during the event of atherogenesis. In addition, the membrane structure of macrophages and the signalling pathways involved in endocytosis integrated with lipid metabolism are detailed. This article establishes future insights into the scavenger receptors as potential targets for cardiovascular disease prevention and treatment.