The rising global demand for rare earth elements (REEs) underscores the need for efficient extraction and recovery techniques. Although the REE industry has employed various techniques, including ion exchange, electrochemical processes, and solvent extraction, there is still a demand for the development of novel solvents that could efficiently extract REEs from water without severe environmental compromise. This paper evaluates hydrophobic deep eutectic solvents (HDESs) for extracting cerium(III)─a representative REE from aqueous solutions by combining trioctylphosphine oxide (TOPO) as a hydrogen bond acceptor (HBA) with environmentally friendly hydrogen bond donors (HBDs) including propanol, dl-menthol, and octanoic acid. The study further explored and discussed cerium(III) extraction behavior under various experimental conditions, including different HDES combinations, HBA-to-HBD ratios, and settling times. The screening charge for the systems was further investigated using COSMO-RS by generating sigma surfaces and sigma potentials. Among the various HDES developed, TOPO/propanol (1:1) exhibited the best extraction efficiency (93.8 ± 1.54%) in a 30 mM cerium(III) nitrate solution. Finally, the mass transfer coefficient for the three solvents was evaluated. The results for TOPO/propanol, TOPO/dl-menthol, and TOPO/octanoic acid were 8.90 × 10–6, 7.05 × 10–6, and 6.14 × 10–7 m·s–1, respectively.