Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology with lung involvement in most cases. The pathological hallmark of sarcoidosis is the formation of non-necrotizing granulomas incited by the accumulation of activated macrophages and T-cells, and the local production of proinflammatory cytokines. Despite their clinical significance to sarcoidosis, the molecular and cellular sequences of events promoting macrophage aggregation and transformation into epithelioid cells that initiate and maintain granulomas remain elusive. We aim to elucidate the molecular mechanisms that activate and regulate granuloma formation in sarcoidosis, by resorting to a translational approach combining cutting-edge research tools, advanced preclinical cellular and animal models, and human patients. In particular, we propose to resolve the immunometabolic signatures that drive granuloma formation, define the contribution of metabolic profiles to immune cell function during granulomatous inflammation; and map novel immunometabolic candidates of genetic susceptibility to sarcoidosis. We expect thus to reveal essential pathogenetic mechanisms underlying granulomatous inflammation, and identify new therapeutic solutions for sarcoidosis.