Background: According to World Health Organization (WHO), adults with a Body Mass Index (BMI) ≥ 30 kg/m² are considered obese, while those with a BMI between 25 and 29.9 kg/m² are classified as overweight. Beyond lifestyle and behavioural factors, an intricate web of physiological mechanisms plays pivotal role in development and persistence of obesity. Understanding these mechanisms is essential for developing effective prevention and treatment strategies. Aim: To examine prevalence trends and pathophysiological mechanisms contributing to global obesity. Methods: A systematic search was conducted across major databases including PubMed, Scopus, and Web of Science using predefined keywords related to obesity and human physiology. Studies published in English from 2000 to 2024 were included. Eligibility criteria focused on original research and high-quality reviews exploring physiological contributors to obesity in humans. The selection process followed PRISMA guidelines. Key Findings: This highlights the prevalence of obesity both globally and in India. It also identifies role of hormonal regulators such as leptin, ghrelin, insulin, and cortisol in appetite and energy metabolism. Neurophysiological centers, particularly hypothalamus, significantly influence hunger and satiety. Adipose tissue acts as an endocrine organ, releasing pro-inflammatory cytokines. Additionally, gut microbiota imbalances have been linked to altered nutrient absorption and metabolic dysfunction. Genetic and epigenetic factors further modulate these physiological pathways, contributing to individual susceptibility. Conclusion: Obesity is a complex, multifactorial condition deeply rooted in human physiology. Addressing its physiological foundations alongside lifestyle interventions may enhance effectiveness of treatment strategies and public health policies.