The direct conversion of methane to methanol offers a promising approach to utilize abundant natural gas resources; however, the finding of suitable low-cost catalysts remains challenging due to the chemical inertness of methane. In this study, we performed a theoretical investigation of the role of transition-metal single-atom catalysts (TM-SACs) anchored on the hydroxyapatite support, where TM = Fe, Co, Ni, and Cu. We examined adsorption properties, formation of oxidized active sites, methane activation, methanol formation, and its stability using density functional theory calculations with van der Waals corrections, combined with the climbing image nudged elastic band method for the localization of transition states. Our findings reveal that Cu/HAP exhibits the most favorable energy profile for the conversion of methane to methanol, offering lower activation barriers and a more exothermic reaction pathway compared to other systems. In contrast, Fe/HAP shows superior oxygen dissociation capabilities but faces challenges in methanol production due to higher reaction barriers. These findings provide valuable information for the future design of TM/HAP catalysts for sustainable methane utilization.