The accuracy of laboratory test outcomes is paramount in clinical diagnostics, guiding crucial decisions in patient care. However, the interference of certain medications and nutritional supplements in laboratory assays can significantly skew results, leading to potential misdiagnoses or inappropriate management strategies. This comprehensive review explores the multifaceted nature of such interferences, examining the mechanisms through which a wide array of pharmaceuticals and over-the-counter supplements can affect the analytical phases of laboratory testing. By highlighting specific instances where common medications and supplements have led to erroneous lab results, the review underscores the importance of clinician awareness and the need for meticulous patient history taking. Furthermore, it discusses current strategies and future directions in minimizing these interferences, including advances in laboratory technology and the integration of electronic health records. This critical examination aims to enhance the interpretation of lab results, ensuring more accurate and effective patient care.