Idiosyncratic drug-induced agranulocytosis is a rare but potentially fatal adverse drug reaction characterized by a sudden and profound drop in neutrophil count, predisposing patients to severe infections. Despite its low incidence, idiosyncratic drug-induced agranulocytosis remains a significant clinical challenge due to its unpredictable onset and the wide array of medications implicated in its occurrence. Traditional management relies on early recognition and immediate drug withdrawal, but preventive strategies have historically been limited. Recent advances in pharmacogenomics have improved our understanding of individual susceptibility, with certain HLA alleles and genetic polymorphisms emerging as key risk factors. The identification of risk clusters—including genetic, demographic, and clinical features—supports more tailored prevention. Big data analytics and artificial intelligence (AI) now offer promising tools for predictive modeling and real-time pharmacovigilance signal detection. Technological innovations such as telemedicine, wearable sensors, and home-based blood cell monitoring enable earlier detection and intervention, especially in high-risk patients. Therapeutic patient education (TPE) plays a crucial role in increasing awareness, promoting adherence to monitoring protocols, and empowering patients in self-management. This review highlights the convergence of scientific, clinical, and technological progress that supports a shift toward a more proactive, personalized, and preventive approach to idiosyncratic drug-induced agranulocytosis management in modern internal medicine.