Bitumen is most commonly used as a binder in road pavement construction. Due to the harsh climate changes and heavier traffic loads, bitumen tends to undergo rutting and cracking which severely limits its service life and durability. Bitumen-based binders containing various proportions of styrene-butadiene-styrene (SBS) triblock copolymer, crumb rubber (CR) and fumed nanosilica have been synthesized. The modified binders have been studied for rheological properties, storage stability, nanoparticle dispersion, and thermal resistance. In addition, binder-sand composites have been prepared in a binder/sand weight ratio of 1:9 and have been tested for three-point flexural bend tests. Addition of nanosilica dramatically improves the rheological properties of bitumen with enhancements as great as 400% and the compatibility between bitumen and polymers is enhanced. In addition, CR-modified bitumen demonstrates a similar level of performance as SBS-modified bitumen, when both are used synergistically with nanosilica, which leads to beneficial environmental and economic impacts. Finally, the interfacial mechanisms between bitumen, polymers and nanosilica that are responsible for modification of bitumen using Fourier-Transform Infrared (FTIR) Spectroscopy and Dynamic Mechanical Analysis (DMA) were investigated and correlated with the performance of the materials.