Resistant arterial hypertension is one of the most challenging forms of hypertension and is associated with a significantly increased risk of cardiovascular complications and mortality. This study examines the theoretical foundations, epidemiological characteristics, and major predictors of resistant arterial hypertension in patients living in the Fergana Valley. Special attention is given to the influence of obesity, metabolic syndrome, diabetes mellitus, chronic kidney disease, and lifestyle-related factors on the development of treatment-resistant hypertension. The study also evaluates the role of environmental and climatic conditions in blood pressure regulation. The findings indicate that resistant hypertension is a multifactorial disorder resulting from complex interactions between metabolic, cardiovascular, and environmental factors. Early identification of major predictors and implementation of comprehensive preventive and therapeutic strategies may improve blood pressure control and reduce the burden of cardiovascular disease.