Urea biosensors are essential for clinical, environmental, and industrial monitoring. However, their widespread application is limited by enzymatic instability, signal interference, and poor operational durability. This study identifies the key design and performance limitations of current urea biosensors and proposes integrated strategies to overcome these challenges. Major issues such as urease instability, enzyme leakage, biofouling, and matrix-induced cross-sensitivity are evaluated. To address these, advanced material approaches including covalent immobilization within nanoporous and metal-organic framework structures, antifouling coatings, and nanocomposite electrodes for operating low potentials are highlighted. The main innovation of this study lies in establishing a unified design framework that integrates material selection, surface chemistry, and signal processing strategies to enhance sensitivity, selectivity, and long-term stability. This holistic approach provides a practical pathway for the development of robust, reliable, and commercially scalable urea biosensor systems.