Interests in learning how to engineer most effective covalent ligands, identify novel functional targets, and define precise mechanism-of-action are rapidly growing in both academia and pharmaceutical industries. We here illuminate the establishment of a multifunctional platform that offers new capabilities to logically engineer covalent ligands and dissect 'on-target' bioactivity with precise biological context and precision hitherto inaccessible. Broadly aimed at non-specialist readers, this opinion piece is aimed to stoke the interest of emerging chemists and biologists/bioengineers, but the underlying technological and conceptual topicality is anticipated to also appeal to experts leading ligand-target mining, validation, and -discovery research programs.