This study investigates optimizing working fluids and system design for Waste Heat Recovery (WHR) in turboelectric aircraft, focusing on the Onera Dragon concept. Using the PC-SAFT equation of state and QSPR models, the research identifies optimal fluids for an Organic Rankine Cycle (ORC)-based airborne WHR system. The method includes optimizing pseudo-fluids, which are mapped to real fluids based on PC-SAFT parameter proximity. A bi-objective optimization also attempts to find real-fluid optima directly. The best pseudo-fluid achieved a 1.56% fuel saving, while the best real fluid, acetyl chloride, achieved 1.37%, outperforming cyclopentane’s 0.92%. The bi-objective approach did not yield better real-fluid results. Binary mixtures of non-polar pseudo-fluids and blends of cyclopropane and cyclopentane showed no improvement, indicating no benefit from temperature glide in the condenser.