Childhood obesity represents an important public health issue worldwide and is strongly linked to metabolic alterations such as hypertension, insulin resistance, and dyslipidemia. The constellation of these conditions is commonly known as Metabolic Syndrome (MetS). Metabolic syndrome is not just a simple cluster of metabolic complications due to excess of adipose tissue, but is considered a risk factor for cardiovascular diseases. Evidence from several human and animal studies suggests that environmental and nutritional exposure during pregnancy may affect the newborn development and future health through epigenetic changes, playing a potential role in determining obesity and obesity-related complications. Understanding how nutritional epigenetic mechanisms contribute to the “transgenerational risk” for obesity and metabolic dysfunction is crucial in order to develop early prevention strategies for children’s health. Nutrigenetics is the science that studies the role of nutrients in gene expression. Long Chain Polyunsaturated Fatty Acids (LCPUFAs) are known for their health benefits, especially in relation to their ability to modulate inflammation and improve some obesity-associated comorbidities, mainly by decreasing plasma triglycerides. Recent nutrigenetic research is focusing on the potential role of LCPUFAs in influencing epigenetic markers. In this review, we present the most recent updates about the possible interaction between n-3 LCPUFAs and epigenetic pathways in metabolic syndrome. Literature from MEDLINE® and the Cochrane database between May 2005 and December 2018 has been scanned.