First principles calculations are performed to study the noncovalent functionalization of single-wall carbon nanotubes (SWCNTs) and boron nitride nanotubes (BNNTs) with pyrazinamide (PZA), an antitubercular chemotherapeutic, providing a detailed insight into the nanotube structure and electronic properties prior to and after functionalization. The simulations highlight the modification in electronic structure of both SWCNTs and BNNTs with the enhancement of electronic states within the valence and conduction band regions of the PZA–SWCNT system, significant lowering of the energy gap and the presence of new dispersionless bands in the PZA–BNNT system. Depending on the chirality of the nanotubes, PZA exhibits a preferential selectivity for adsorption, which is further affirmed from the band structure, density of the states, total projected density of the states and frontier orbital analysis with a charge transfer between PZA and a nanotube. A molecular docking simulation suggests that SWCNTs facilitate the targeted release of PZA within the protein through a lock and key mechanism. The intermolecular interaction between PZA–SWCNT and pncA was compared using a molecular dynamics simulation, and by observing any structural change induced within the system due to the interactions. Thus, functionalization of SWCNTs and BNNTs with PZA mediated by π–π stacking is an effective method to engineer nanotubes’ electronic properties and band gaps for applications pertinent to tuberculosis chemotherapy.