Obesity is a significant global health challenge, increasing the risk of chronic conditions such as diabetes, cardiovascular disease, and hypertension. Endoplasmic reticulum stress (ERS) plays a crucial role in the metabolic dysregulation associated with obesity by modulating metabolism, insulin signaling, inflammation, and cell proliferation and death through the unfolded protein response (UPR) pathway. This review comprehensively explores the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, highlighting its role as a bridge between adipose tissue functionality and the inflammatory response. The article discusses the interaction between ERS and adipose tissue, including the regulation of lipogenesis, the impact of adipose tissue dysfunction on ERS, and the crosstalk between adipose tissue inflammation and ERS. It also examines the inflammatory cascade mediated by ERS through the UPR pathway, involving key signaling pathways such as JNK, IKK, and NF-κB. Finally, the review explores potential therapeutic approaches targeting ERS to treat obesity and its associated metabolic disorders, including WATME-specific immunotherapy, nanoparticle therapy, and the use of miRNAs and ERS inhibitors. Understanding the molecular pathways involved in ERS and its connection to obesity and its sequelae is crucial for developing targeted interventions to combat obesity and its complications.Obesity is a significant global health challenge, increasing the risk of chronic conditions such as diabetes, cardiovascular disease, and hypertension. Endoplasmic reticulum stress (ERS) plays a crucial role in the metabolic dysregulation associated with obesity by modulating metabolism, insulin signaling, inflammation, and cell proliferation and death through the unfolded protein response (UPR) pathway. This review comprehensively explores the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, highlighting its role as a bridge between adipose tissue functionality and the inflammatory response. The article discusses the interaction between ERS and adipose tissue, including the regulation of lipogenesis, the impact of adipose tissue dysfunction on ERS, and the crosstalk between adipose tissue inflammation and ERS. It also examines the inflammatory cascade mediated by ERS through the UPR pathway, involving key signaling pathways such as JNK, IKK, and NF-κB. Finally, the review explores potential therapeutic approaches targeting ERS to treat obesity and its associated metabolic disorders, including WATME-specific immunotherapy, nanoparticle therapy, and the use of miRNAs and ERS inhibitors. Understanding the molecular pathways involved in ERS and its connection to obesity and its sequelae is crucial for developing targeted interventions to combat obesity and its complications.