This mini-review highlights some recent progress in the engineering of single-atom catalysts (SACs) through metal–organic frameworks (MOFs) and derivatives. The inherent molecular and chemical specificities within the MOFs and derivatives can offer stabilisation of the SACs with high atomic isolation and dispersion. As MOFs are often considered an infinite array of self-assembled molecular catalysts, specifically designed structures can provide further functionalities to suit the needs of different catalytic applications. In brief, we can divide the preparation approaches into three main categories: (1) fabrication onto functional groups of the ligands, (2) fabrication onto Lewis acid sites of nodal centres, and (3) synthesis via a pyrolysis-mediated technique. Through these approaches, strong metal–support interactions can be established to aid the fine-tuning of the catalytic properties. We also discuss how recent progress in the development of state-of-the-art microscopic, spectroscopic, and crystallographic techniques has enabled scientists to elucidate the structure–activity relationship.