Treatment-Resistant Schizophrenia (TRS) is a severe condition affecting up to 30% of individuals with schizophrenia, characterized by poor response to standard antipsychotics and leading to substantial clinical and economic burdens. Clozapine is the only antipsychotic consistently shown to be effective in managing TRS. This review aims to evaluate the role of clozapine in improving clinical outcomes, quality of life, and cost-effectiveness for TRS patients. A narrative literature review was conducted by analyzing seven peer-reviewed studies published globally, including longitudinal, cohort, and cross-sectional designs. Results indicate that clozapine significantly reduces both positive and negative symptoms, improves psychological and social functioning, and lowers the frequency of hospitalization and emergency visits. Furthermore, caregivers reported reduced stress and economic burden. Despite the necessity for regular monitoring due to potential adverse effects, the long-term benefits of clozapine, including better quality of life and reduced healthcare costs, outweigh its risks. Clozapine also demonstrates unique pharmacological properties that contribute to its effectiveness beyond dopamine antagonism. In conclusion, clozapine remains the most effective treatment for TRS, offering superior clinical efficacy, patient satisfaction, and cost savings, thus supporting its prioritized use in psychiatric practice for individuals unresponsive to conventional therapy.