This paper investigates the intricate relationship between macronutrient composition and energy balance in human metabolism. With the rising prevalence of obesity and metabolic disorders, understanding the effects of different macronutrient ratios on energy intake, expenditure, and overall health is of paramount importance. Through a systematic review of existing literature, controlled feeding experiments, and mathematical modeling, this study provides insights into how carbohydrates, proteins, and fats impact energy homeostasis. The findings reveal that macronutrient distribution plays a pivotal role in regulating weight and metabolic health. Low-carbohydrate diets may promote short-term weight loss, high-protein diets enhance satiety and thermogenesis, and the quality of dietary fats influences metabolic outcomes. However, the long-term effects and individual variability necessitate further investigation. This study contributes to a comprehensive understanding of macronutrient-mediated energy balance and underscores the need for balanced dietary approaches for optimal health.