Atherosclerosis is a chronic and multifactorial disease of the arterial wall that evolves through a complex interplay of biochemical, cellular, and molecular mechanisms. The present study investigates the progressive stages of atherosclerosis, emphasizing the roles of oxidative stress, lipid metabolism, inflammatory mediators, and endothelial dysfunction. Our observational study analyzed 300 patients stratified into four clinical groups—control, early, moderate, and severe atherosclerosis—based on diagnostic imaging, clinical scoring, and biochemical profiling. The study incorporated advanced biomarker analysis, histological tissue examination, and enzyme activity assessment. Results demonstrated significant correlations between oxidized LDL, proinflammatorycytokines such as IL-6 and TNF-alpha, and suppressed endothelial nitric oxide synthase (eNOS) activity. These findings underline the need for a systems biology approach to detect, predict, and intervene in the progression of atherosclerosis, offering new insights for targeted therapies.