This study investigates the combined impact of Trinidad Lake Asphalt (TLA) and styrene–isoprene–styrene (SIS) on the performance of PG 64-22 asphalt binder. The study specifically examines how the addition of TLA and SIS affects the stiffness, viscoelastic properties, and ability to resist deformation of the asphalt binder, using the Superpave test method. The findings demonstrate that the addition of SIS improves the ability to withstand deformation, with the best results seen in the mixture containing 20% TLA and 5% SIS. This blend achieves a harmonious combination of stiffness, pliability, and ease of use. Increasing the SIS content to 10% and combining it with a 20% TLA greatly enhances resistance to rutting, but it also decreases workability. In addition, a mixture consisting of 10% TLA and 10% SIS provides excellent resistance to fatigue and possesses viscoelastic properties that are well suited for reducing oxidative aging and cracking. Although SIS typically enhances the performance of binders, an excessive quantity can result in unwanted rigidity, requiring meticulous optimization. The results highlight the importance of customizing TLA–SIS combinations according to specific environmental conditions in order to optimize advantages. Subsequent studies should investigate the prolonged impacts and alternative combinations of additives to further improve the performance of binders.