Increasing trace levels of antibiotics and hormones in the environment and food samples are concerning and pose a threat. Opto-electrochemical sensors have received attention due to their low cost, portability, sensitivity, analytical performance, and ease of deployment in the field as compared to conventional expensive technologies that are time-consuming and require experienced professionals. Metal-organic frameworks (MOFs) with variable porosity, active functional sites, and fluorescence capacity are attractive materials for developing opto-electrochemical sensors. Herein, the insights into the capabilities of electrochemical and luminescent MOF sensors for detection and monitoring of antibiotics and hormones from various samples are critically reviewed. The detailed sensing mechanisms and detection limits of MOF sensors are addressed. The challenges, recent advances, and future directions for the development of stable, high-performance MOFs as commercially viable next-generation opto-electrochemical sensor materials for the detection and monitoring of diverse analytes are discussed.