This systematic study was conducted on the separation of yttrium (Y) and erbium (Er) from a chloride medium using a mixed extractant system composed of [N1444][P507] and TRPO (trialkylphosphine oxide) in kerosene. This investigation focused on the effects of various extractants, extraction systems, the initial acidity of the aqueous phase, and the phase contact time on the extraction efficiencies of Y and Er. This study showed that using the combination of [N1444][P507] and TRPO notably increased the extraction performance and enhanced the separation factor between Y and Er, outperforming the individual use of P507 or [N1444][P507] under identical conditions. The extraction efficiencies for Y and Er reached 88.4% and 93.3%, respectively, with a separation factor (Er/Y) of 1.84, highlighting the system’s effectiveness in selectively isolating rare earth elements. Optimal stripping conditions were obtained using 0.1 mol/L of HCl, resulting in a successful recovery of 93.1% of Y3+ and 78.9% of Er3+ from the organic phase. The extraction mechanism involved both ion exchange and ion association. The enthalpy changes (ΔH) associated with the extraction of Y3+ (−2.5 kJ·mol−1) and Er3+ (4.6 KJ·mol−1) demonstrate that the extraction processes are exothermic, reflecting the thermodynamic differences between the two ions.