The increasing utilization of hydrazine and its derivatives across diverse sectors highlights the pressing need for efficient detection methods to safeguard human health and the environment. Likewise, nicardipine, a widely used medication for heart diseases, necessitates accurate sensing techniques for clinical research and therapeutic monitoring. Here, we propose a novel approach using a naphthalimide-functionalized Zr-MOF as a fluorometric probe capable of detecting both hydrazine and nicardipine in aqueous medium. Our designed probe exhibited a significant 31-fold increase in fluorescence intensity upon interaction with hydrazine. At the same time, nicardipine induced 86% fluorescence quenching with an exceptionally rapid response time (100 s for hydrazine and 5 s for nicardipine). The designed probe has the ability to detect both analytes at nanomolar concentrations (LOD for hydrazine is 1.11 nM while that for nicardipine is 9.6 nM). Investigation across various wastewater samples and pH conditions further validated its practical utility. The mechanism behind fluorometric sensing of nicardipine was thoroughly investigated using modern instrumentation. Our study presents a versatile and effective approach for detecting hydrazine and nicardipine, addressing crucial needs in both industrial and biomedical contexts.