Metal–organic frameworks (MOFs), owing to their high specific surface area, tunable porosity, extensive structural diversity, and versatile functionalization capability, have emerged as one of the most important classes of advanced materials in the field of electrochemical sensing. Their ability to establish specific interactions with target analytes enables highly sensitive and selective detection of environmental pollutants, pharmaceutical compounds, heavy metals, and biomarkers. Nevertheless, several limitations, including low intrinsic electrical conductivity, limited stability in aqueous media, and challenges associated with large-scale production, have hindered their widespread practical application. This review examines the major strategies employed to enhance the performance of MOF-based electrochemical sensors, including nanostructuring approaches, the development of MOF-derived nanocomposites, the design of bimetallic MOFs, and various structural functionalization techniques. Furthermore, recent applications of these sensors in the detection of emerging contaminants, pharmaceutical compounds, heavy metals, and biological markers are comprehensively discussed. In addition, the role of artificial intelligence (AI) and machine learning (ML) in the design of novel sensing materials, electrochemical data analysis, and the development of intelligent sensing platforms is highlighted. The findings indicate that the integration of MOFs with conductive nanomaterials, wearable sensing systems, the Internet of Things (IoT), and AI-driven algorithms can accelerate the development of next-generation electrochemical sensors. Despite persistent challenges related to stability, scalability, and commercialization, recent advances demonstrate the significant potential of MOFs for the development of intelligent monitoring systems in environmental surveillance, food safety, and healthcare applications.