Nutrigenomics investigates how nutrients interact with genes to affect health outcomes. Among these nutrients, omega-3 fatty acids, especially EPA and DHA, have been identified as significant dietary elements that can modulate gene expression linked to inflammation. Since inflammation plays a crucial role in metabolic syndrome (MetS), understanding the molecular and nutrigenomic mechanisms by which omega-3s influence inflammatory gene expression is essential. This review examines recent developments in the role of omega-3 fatty acids in regulating inflammatory pathways related to MetS, drawing on evidence from clinical trials, molecular studies, and personalized nutrition approaches to demonstrate the potential for specific nutritional interventions.