This study investigated the synergistic effects of hydrated lime (HL) and soybean oil (SO) as additives in warm mix asphalt (WMA) to improve moisture resistance using the extreme vertices design approach. The main factors considered were the proportions of HL, SO, and bitumen, expressed as percentages of bitumen content, while the aggregate composition remained constant. Moisture resistance was assessed using the tensile strength ratio (TSR). Key findings include: TSR values ranged from 76.06% to 94.71%, with many samples meeting the AASHTO-required 80%. HL had the greatest impact on TSR, with moderate SO levels improving TSR, but excessive SO decreasing it. The strongest interaction affecting TSR was between HL and SO, while bitumen’s role was less influential. The regression model for TSR had an R² of 93.09%, indicating a strong predictive capacity. Optimized mixture proportions were 5.77% bitumen, 0.08% soybean oil, and 0.10% hydrated lime, targeting a TSR of 80%, which meets AASHTO guidelines. The study emphasized the importance of balancing additives to enhance moisture resistance while minimizing bio-based additives.