Obesity, metabolic syndrome, and osteoarthritis (OA) require integrative understanding and management. This review highlights the complex interplay between obesity, metabolic syndrome, and OA, emphasizing the roles of adipokines, inflammation, and metabolic dysregulation in OA pathogenesis. Obesity contributes to mechanical joint overload and metabolic dysregulation, increasing OA risk, particularly in the knee. Metabolic syndrome exacerbates these risks through chronic inflammation and altered macrophage activity. Adipokines such as leptin, adiponectin, resistin, visfatin, and chemerin play critical roles in OA progression by modulating inflammation, cartilage degradation, and joint homeostasis. Obesity and metabolic syndrome alter adipokine levels, promoting pro-inflammatory pathways and impairing chondrocyte function. These conditions disrupt joint structure and function, leading to OA progression. Interventions targeting adipokine modulation, macrophage polarization, and chondrocyte function may offer therapeutic strategies for OA. The review underscores the need for integrated approaches to manage obesity, metabolic syndrome, and OA, considering both mechanical and biochemical factors. Future research should focus on understanding the complex interactions between adipokines, inflammation, and joint health to develop effective therapies for OA.Obesity, metabolic syndrome, and osteoarthritis (OA) require integrative understanding and management. This review highlights the complex interplay between obesity, metabolic syndrome, and OA, emphasizing the roles of adipokines, inflammation, and metabolic dysregulation in OA pathogenesis. Obesity contributes to mechanical joint overload and metabolic dysregulation, increasing OA risk, particularly in the knee. Metabolic syndrome exacerbates these risks through chronic inflammation and altered macrophage activity. Adipokines such as leptin, adiponectin, resistin, visfatin, and chemerin play critical roles in OA progression by modulating inflammation, cartilage degradation, and joint homeostasis. Obesity and metabolic syndrome alter adipokine levels, promoting pro-inflammatory pathways and impairing chondrocyte function. These conditions disrupt joint structure and function, leading to OA progression. Interventions targeting adipokine modulation, macrophage polarization, and chondrocyte function may offer therapeutic strategies for OA. The review underscores the need for integrated approaches to manage obesity, metabolic syndrome, and OA, considering both mechanical and biochemical factors. Future research should focus on understanding the complex interactions between adipokines, inflammation, and joint health to develop effective therapies for OA.