<p>Metal–Organic Frameworks (MOFs), characterized by their high porosity, large surface area, and structural tunability, have emerged as highly promising materials for the development of advanced sensing platforms. Composed of metal ions or clusters linked by organic ligands, MOFs offer unique opportunities in the detection of veterinary antibiotics, a pressing concern owing to the overuse of these drugs in agriculture, aquaculture, and livestock. The accumulation of antibiotic residues such as tetracyclines, sulfonamides, nitrofurans, and fluoroquinolones in food and water sources poses serious public health risks, including antimicrobial resistance and chronic toxicity. While traditional analytical techniques like Liquid Chromatography-Mass Spectrometry (LC–MS), Enzyme-Linked Immunosorbent Assay (ELISA)) are sensitive, they are often time-intensive, costly, and unsuitable for field applications. In contrast, MOF-based sensors offer rapid, portable, and highly selective detection through mechanisms such as fluorescence quenching, electrochemical redox reactions, and colorimetric responses via peroxidase-like activity. This review provides a detailed account of recent advancements in the design, synthesis, and application of MOFs and their composites for antibiotic detection, with an emphasis on fluorescence and colorimetric sensing strategies. It also critically evaluates existing challenges related to real-sample interference, sensor regeneration, and detection limits, concluding with future prospects for integrating MOF-based sensors into portable diagnostic platforms for real-time monitoring of antibiotic residues in environmental and food samples.</p>