The need for desalination has increased as freshwater supplies decline. Low-grade heat sources such as solar photovoltaic thermal can operate membrane distillation. In this article, solar thermal sources, and vacuum-enhanced direct contact membrane distillation configurations are analyzed to assess how well photovoltaic thermal fits the process. Integrating photovoltaic-thermal systems with vacuum-enhanced direct contact membrane distillation provides an innovative, efficient, and technically better option. The research analyzed and simulated this integrated system’s performance in MATLAB. According to the findings, the efficiency of vacuum-enhanced direct contact membrane distillation systems driven by photovoltaic thermal technology is greatly enhanced when the feed water temperature is raised. The efficiency of evaporation and permeate flow showed a significant improvement, increasing from 43 to 48%. At the same time, there was a significant decrease in the specific thermal energy consumption from 1170 kWh/m3 to 890 kWh/m3 because the feed water temperature was increased from 36 °C to 48 °C and energy from a photovoltaic system was used. The results indicate that the vacuum-enhanced direct contact membrane distillation system has an increase in performance compared to the direct contact membrane distillation system under identical operating conditions for freshwater production.