Plasmon-induced chemistry, which harnesses the energy of the collective oscillations of conduction electrons in metallic nanoparticles (NPs) upon light irradiation, has become a powerful tool for driving chemical reactions under mild conditions. This field shows great potential for applications ranging from catalysis and energy conversion to sensing and biomedicine. Plasmonic catalysts can be viewed as complete reactors, since all light-initiated processes can influence the reaction pathway. For example, the plasmonic electric field can attract and orient molecules, while energetic charge carriers (electrons and holes) and localized heating from plasmon excitation can trigger redox reactions or lower the activation energy of other processes, facilitating chemical transformations that would otherwise be unfavorable.[1] While several aspects of plasmon-enhanced reactions are well understood, a critical gap remains in our understanding of the initial steps, specifically the role of molecular adsorption on the metallic nanoparticle surface and its influence on subsequent photoreactivity. Existing literature often treats the adsorption process in a simplistic manner, neglecting the intricacies of surface coverage, molecular orientation, and surface complex formation.[1] Most studies use thiols to perform such experiments; however, thiols are strong directing agents and do not reproduce the complexities of a free molecule interacting with a metal surface. This study investigates the complex interaction between the adsorption of halogenated adenines, specifically 2- and 8-halogen adenine, as well as 8-halogen adenosine, on gold and silver nanoparticles, and their subsequent reactivity. We show that the adsorption configuration and the molecule-surface orientation differ significantly between gold and silver nanoparticles. The results show that the molecule's orientation strongly affects the reaction rate in gold nanoparticles, whereas in silver, the overall reaction proceeds very efficiently, independent of the molecule. These results are supported by Raman spectra simulated using density functional theory of the molecules adsorbed on metal clusters. Our results show that molecules with multiple interaction points can be activated by plasmonic nanoparticles, but the reaction outcome is still dependent on the leaving group orientation; if it is closer to the metal surface, the reaction is suppressed. By establishing this link between the orientation of halogenated adenines and reaction outcome, we can go beyond purely experimental methods and develop design principles for highly effective plasmonic catalysts tailored to specific bio-related applications.