Obesity is the driving force behind many chronic conditions including the metabolic syndrome, hypertension (HTN), cardiovascular disease (CVD), type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD). With the increasing prevalence of obesity and its associated comorbidities, there is growing interest in understanding the underlying pathophysiology linking obesity to cardiovascular dysfunction and impaired glucose homeostasis. Resistance to the metabolic actions of insulin plays a critical role in the pathogenesis of obesity-associated metabolic diseases. The mechanisms underlying obesity-induced insulin resistance and cardiovascular dysfunction remain to be fully understood. However, dysfunctional adipose tissue plays a critical role and there is mounting evidence demonstrating its role in dysregulation of immunity, inflammation, oxidative stress, endoplasmic reticulum stress and abnormalities in gut microbiota. A better understanding of the underlying pathogenesis of obesity and its link to insulin resistance will help us in the development of innovative and more effective interventions. In this review, we will explore factors such as inflammation, oxidative stress, endoplasmic reticulum stress, renin-angiotensin-aldosterone system, and immune responses that mediate insulin resistance in obesity-associated metabolic diseases. Further, we will also discuss current management options and their clinical implications.