Our study demonstrates for the first time that antigen-binding proteins with immunoglobulin fold, such as nanobodies, can be engineered to directly bind metals frequently used in cancer diagnostics (imaging) and therapeutics. Only one or two mutations of protein residues are sufficient to create a binding motif that buries the metal in the protein’s interior. We demonstrate this for the three main group metals gallium, indium and bismuth, covering most theranostic applications as well as applications in chemical biology, such as single-cell mass cytometry. Our strategy not only overcomes the need for expensive and non-selective bifunctional linkers connecting immunoglobulins with large chemical chelators, but also makes metal-bioconjugates fully accessible via biotechnological production. Moreover, our labelling strategy is quantitative, with full uptake of the metal within a few minutes, and the labelled nanobodies maintain their natural folds. This, coupled with burying the metal in the protein core enables the metal-bound nanobodies to remain stable for weeks. Importantly, the metal-bound nanobodies are resistant to competition from endogenous metal binders like glutathione, and retain functionality.