This study presents a proof-of-concept investigation of a tapered side-hole optical fiber (S-H OF) functionalized with DNA–surfactant biopolymer coatings for vapor sensing. The functionalized fiber was investigated in the 1200–1800 nm spectral range under fixed exposure conditions using vapors generated from 200 µL of aqueous ammonia (NH₃·H₂O) and trimethyl phosphate (TMP). Two functional coatings, DNA–DODA and DNA–(S)–TMA, were compared to evaluate their influence on the spectral response of the tapered fiber. Under the investigated exposure conditions, the DNA–DODA coating exhibited the largest optical power variation during exposure to NH₃·H₂O vapors, reaching ΔOP = 3.84 dB at approximately 1463 nm and 1.75 dB at approximately 1504 nm. In contrast, DNA–(S)–TMA exhibited a stronger response to TMP vapors, with ΔOP = 1.19 dB at approximately 1510 nm and 2.46 dB at approximately 1780 nm. These results demonstrate that the choice of DNA–surfactant coating may influence the optical response of the tapered S-H OF under fixed vapor-exposure conditions. The present study focuses on comparing the responsiveness of the investigated DNA–surfactant coatings, providing a basis for the further development of the proposed sensing platform. Future studies will focus on comprehensive sensor characterization under controlled analyte concentrations, including the determination of sensitivity, dynamic range, limit of detection and long-term stability.