Macrophages are essential immune cells in all tissues and are vital for maintaining tissue homeostasis, immune surveillance, and immune responses. Considerable efforts have identified shared and tissue-specific gene programs for macrophages across organs during homeostasis. This information has dramatically enhanced the understanding of tissue-restricted macrophage programming and function. However, few studies have addressed the overlapping and tissue-specific responses of macrophage subsets following inflammation. One subset of macrophages observed across several studies, lipid-associated macrophages (LAMs), have gained interest due to their unique role in lipid metabolism and potential as a therapeutic target. LAMs are associated with regulating disease outcomes in metabolically related disorders including atherosclerosis, obesity, and metabolic dysfunction-associated steatotic liver disease. We utilized single-cell RNA sequencing datasets to profile LAM diversity across multiple tissues and inflammatory conditions in mice and humans, to define a shared LAM transcriptional profile, including Trem2 and Lpl, and sets of tissue-specific gene programs. Importantly, LAM markers were highly conserved with human LAM populations that emerge in inflammation. Overall, this analysis provides a detailed transcriptional landscape of tissue-restricted and shared LAM gene programs, data that may help instruct appropriate molecular targets for broad or tissue-restricted therapeutic interventions to modulate LAM populations in disease.