Azeotropic mixtures such as acetone–chloroform present considerable challenges to conventional separation methods due to their constant boiling behavior, which limits the effectiveness of ordinary distillation techniques. Overcoming these limitations often requires the use of entrainers to break the azeotrope and enhance component separation. However, understanding the interplay between temperature, entrainer type, and the quantity introduced remains a key challenge in optimizing separation performance. This study investigates the flash distillation of an acetone–chloroform binary azeotrope using process modeling and simulation to evaluate how operating temperature and entrainer concentration (introduced via flow rate) affect the separation efficiency. Two entrainers were assessed—water and a secondary organic compound—with simulations conducted across varying temperatures and entrainer dosages. The results reveal that temperature changes have a greater impact on separation efficiency when an entrainer is present, with higher entrainer concentrations significantly enhancing phase separation and making the system less sensitive to temperature fluctuations. Among the entrainers examined, water consistently outperformed the alternative by improving the ease and extent of separation. These findings highlight the critical role of entrainer selection and dosing strategy in azeotropic separation via flash distillation. The insights gained offer a practical basis for improving process design, reducing energy demand, and enhancing product purity in both industrial and research applications. The modeling approach also provides a cost-effective tool for screening and optimizing separation strategies for similar complex mixtures.