1,2,3-triazole system is readily obtained by the click reaction in a facile and regioselective way. Regioselectivity is introduced under Copper(CuAAC), and Ruthenium(RuAAC) catalysed azidealkyne cycloaddition reaction furnishing 1,4 and 1,5-disubstituted triazoles, respectively. These two regioisomeric systems offer discrete physicochemical and medicinal properties based on crucial binding interactions and biocompatibility with the biological targets. In this regard, a comparative investigation on the coumarin-linked regioisomeric 1,2,3-triazoles via its crystal structure, Hirshfeld surface analysis, and antitubercular assays and molecular docking are reported. It sheds light on the variation of in vitro antitubercular efficacy against Mycobacterium tuberculosis H 37 Rv followed by molecular docking studies that justify the prominent interactions at the binding site. Further, solid-state and Hirshfeld surface analysis provided significant crystallographic insights on the critical intermolecular interactions that dictate the crystal packing in these systems. Thus structure-property correlation for these regioisomeric systems can open new avenues in drug design and discovery.