A significant proportion of the global population is affected by obesity, hypertension, diabetes, or cardiovascular disease. These interrelated conditions collectively fall under metabolic syndrome. This cluster of metabolic risk factors, including obesity, hypertension, insulin resistance, and dyslipidemia, together increase the risk of cardiovascular diseases and type 2 diabetes mellitus. The global prevalence of metabolic syndrome has been steadily increasing worldwide, which necessitates effective treatment and management strategies. Conventional treatment methods mainly include medications and lifestyle modifications through global dietary recommendations, which often follow generalized approaches and fail to yield optimal outcomes for all individuals. In some cases, they may even result in adverse effects. This highlights the need for personalized microbiome-based therapies for the effective treatment and management of metabolic syndrome and reduce the risks of cardio-metabolic diseases. As microbiome-based therapies are based on gut composition, which is now recognized as a key regulator of metabolism and inflammation in the host, a personalized approach can more effectively address individual variations and optimized treatment outcomes for metabolic syndrome. The current chapter focuses on personalized microbiome-based therapies including probiotics, prebiotics, dietary interventions, and fecal microbiota transplant as therapeutic solutions for treatment and management of metabolic syndrome and cardio-metabolic diseases.