This study aims to investigate and optimize the combined effects of polyphosphoric acid (PPA) and Sasobit additives on the mechanical and performance-related properties of rubberized asphalt binders with ARB58 and ARB64 grades. Using the Response Surface Methodology (RSM) in conjunction with an extensive experimental program, the simultaneous influence of PPA, ground tire rubber (GTR), and Sasobit was evaluated under two distinct scenarios. In the first scenario, asphalt binders with performance grades PG58-22 and PG64-22 were modified with GTR and PPA, while in the second scenario, the same binders were further modified with 2% Sasobit under warm mix asphalt (WMA) conditions. Key performance indicators, including G*/sinδ, m-value, non-recoverable creep compliance (Jnr), and fatigue life, were measured to assess the effectiveness of the modifiers. The results confirmed the significant role of PPA and Sasobit in enhancing fatigue resistance and resistance to permanent deformation. Experimental findings revealed that the incorporation of PPA and Sasobit into the softer binder (ARB58) led to a substantial improvement in fatigue resistance and thermal performance, particularly under low strain levels typically associated with thick pavement structures. The developed RSM-based models demonstrated high predictive accuracy for optimal binder compositions, with an average error of less than 10%. From a performance-oriented optimization perspective, the optimal additive contents for ARB58 were identified as 1.49% PPA and 0.97% Sasobit, while for ARB64, the optimal values were 1.50% PPA and 0.88% Sasobit. These combinations resulted in increased stiffness, enhanced fatigue resistance, and improved low-temperature performance. In the economic optimization scenario, reducing the additive contents to approximately 1.18% PPA and 0.59% Sasobit for ARB58 and 1.16% PPA and 0.55% Sasobit for ARB64 maintained acceptable performance levels while significantly lowering modification costs.