Metabolic disorders such as obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) are increasingly characterized by chronic low-grade inflammation, underpinned by complex molecular signalling events. Central to this inflammatory cascade are eicosanoids and other bioactive lipids—lipid mediators derived enzymatically from arachidonic acid (AA) and other polyunsaturated fatty acids (PUFAs). This chapter provides an in-depth analysis of the molecular mechanisms by which eicosanoids—including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), lipoxins (LXs), resolvins (Rvs), and protectins (PDs)—regulate immune cell activation, cytokine expression, and intracellular signalling pathways in metabolically active tissues. We dissect the roles of key biosynthetic enzymes such as cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 (CYP) oxidases, and examine how their activity is modulated by redox sensitive signalling intermediates and reactive oxygen species (ROS). Special emphasis is placed on the dynamic interplay between lipid mediator networks and key molecular pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptors (PPARs) in metabolic inflammation. The chapter also highlights emerging data on the spatiotemporal regulation of lipid mediator biosynthesis, receptor-specific signalling, and resolution-phase lipidomics. Collectively, we present a systems-level view of how bioactive lipids modulate inflammation at the molecular level and offer perspectives on their potential as therapeutic targets for metabolic diseases.