New aromatic molecule–seed particle interactions are examined and exploited to control and guide seed-mediated gold nanorod (Au NR) growth. This new approach enables better understanding of how small molecules impact the synthesis of metallic nanostructures, catalysing their use in various biomedical applications, such as plasmonic biosensing. We perform experimental studies and theoretical molecular simulations using a library of aromatic molecules where we take advantage of the chemical versatility of the molecules with varied spatial arrangements of electron donating/withdrawing groups, charge, and Au-binding propensity. Au NR growth is regulated by two principal mechanisms, producing either a red or blue shift in the longitudinal localized surface plasmon resonance (LLSPR) peaks. Aromatic molecules with high redox potentials produced an increase in NR aspect ratio and red shift of LLSPR peaks. In contrast, molecules that strongly bind gold surfaces resulted in blue shifts, demonstrating a strong correlation between their binding energy and blue shifts produced. Through enzymatic conversion of selected molecules, 4-aminophenylphosphate to 4-aminophenol, we obtained opposing growth mechanisms at opposite extremes of target concentration, and established a chemical pathway for performing plasmonic ELISA. This unlocks new strategies for tailoring substrate design and enzymatic mechanisms for controlling plasmonic response to target detection in biosensing applications.