End-Stage Renal Disease (ESRD) represents the terminal stage of chronic kidney disease (CKD), marked by irreversible loss of kidney function and a glomerular filtration rate (GFR) of less than 15 mL/min/1.73 m². This life-threatening condition necessitates renal replacement therapies, such as dialysis or kidney transplantation, to sustain life. The etiology of ESRD is multifactorial, with diabetes mellitus, hypertension, and glomerulonephritis being leading causes. Patients often present with symptoms like fatigue, fluid retention, and altered urinary output. Diagnosis relies on laboratory markers, imaging, and sometimes biopsy. Effective management includes dialysis, pharmacological interventions, dietary modifications, and ultimately transplantation. Additionally, addressing complications such as cardiovascular disease, anemia, mineral-bone disorders, and infections is critical. Despite significant morbidity and mortality, multidisciplinary care and early intervention can improve outcomes and quality of life. This review emphasizes comprehensive ESRD management, highlights novel therapeutic approaches, and underscores the importance of prevention through early risk factor control.