Fe-rich smectite clays such as nontronite are widespread on Mars and serve as mineralogical archives of early aqueous processes and potential habitats. Their layered structures, high surface areas, and redox-active Fe sites make them promising candidates for adsorption, preservation, and catalytic transformation of organics. While clay–organic interactions have been extensively studied for Al-rich smectites, the role of Fe-rich clays in preserving nucleobases remains poorly constrained under Mars-like geochemical conditions. Here, we investigated adenine adsorption on nontronite across pH 1.8–13 and temperatures from −100 to 20 °C using Raman, UV–vis, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Raman analyses revealed diagnostic adenine bands in nontronite, including the purine ring-breathing mode at 723 cm–1 and a doublet near 1310–1345 cm–1, persisting under acidic and cryogenic conditions. UV–vis and DLS showed enhanced adenine uptake and aggregation at low pH, declining toward neutral and moderately alkaline conditions. Adsorption remained minimal above pH 11, and the observed spectral changes were primarily attributed to pH-induced modifications of the nontronite surface and possible adenine self-association. SEM confirmed compact, sheet-like morphologies at acidic pH, contrasting with disaggregated, amorphous textures under alkaline conditions, consistent with adenine desorption and partial clay destabilization. Our results demonstrate that adenine adsorption on nontronite is strongly pH- and temperature-dependent, with acidic and cryogenic environments enhancing preservation and spectral detectability. These findings establish the first experimental framework for adenine–nontronite interactions under Mars-like temperatures, while also providing reference Raman fingerprints and mechanistic insights relevant to both planetary exploration and clay–organic processes in terrestrial environments.