Antibiotic residues in foods are a global threat and one of the main reasons for the antibiotic resistance development in bacteria as reported by WHO and many other agencies. Antibiotics are used for the prevention and treatment of various diseases in humans and animals. They are employed to improve the growth rate and feed efficiency in livestock predominantly. The global antibiotic usage in food animals including aquaculture is increasing rapidly and is estimated to increase by 67% by 2030. Due to a lack of adherence to proper dosage protocols, various antibiotic residues have become increasingly prevalent in food products obtained from livestock that are meant for human consumption. Moreover, these complex antibiotic residues can cause chronic toxicity resulting in public health and environmental crises. Hence it is important to detect these residues in the food supply chain for food safety and public health. Metal–organic frameworks (MOFs) are a class of porous hybrid nanomaterials formed by networks of inorganic metal ions or metal clusters with mono-, bi-, and multi-dentate interlinked organic pliable electron-donating ligands and/or linkers. Owing to their atomic-level structural uniformity, tunable porosity, high surface area, flexibility in network topology, high density of active chemical sites, high chemical catalytic activity, etc., these MOF-based nanomaterials can exhibit unique physical, chemical, and mechanical properties highly useful for sensing platforms. Developing nanomaterial-based sensors to identify and detect major antibiotic residues like beta-lactams, tetracyclines, macrolides, aminoglycosides, amphenicols, etc., in consumer foods is of growing interest and MOF nanomaterial-based optical or electrochemical transduction sensors have been reported to show promising performance for antibiotic residue detection as an alternative to conventional techniques. Thus, this review presents the different classes of MOF-based nanomaterials and their synthesis, structure, functionalization, and sensing methodology to design a robust antibiotic residue detection sensor mainly useful in the food sector (including water). The discussions also extend to challenges and future research to be conducted to make these materials suitable for rapid testing of food samples along the food supply chain to establish a safer, secure, and sustainable food system.