We will discuss grand challenges for the future cyberinfrastructure, the role of photonics in nanoscale and exascale systems, and intelligent heterogeneous multi-domain networking. In particular, we will discuss 2D and 3D heterogeneous integration and their impacts on future cyberinfrastructures. The talk will be in three parts addressing applications in future networking, computing, and imaging systems with signal processing capabilities in temporal, spectral, and spatial domains. Heterogeneous integration technologies involving silicon, silica, III -V, II-VI, lithium-niobate, and many other related material systems helped realize microsystems with new photonic, electronic, and magnetic functionalities combined together in compact packages. In addition to electronic 3D-ICs currently in rapid development, the newly emerging 3D photonic integrated circuit (PIC) includes arbitrarily shaped waveguides inscribed by femtosecond lasers. Heterogeneous integration utilizing wafer bonding, hetero-epitaxy, and self-assembly offers methods for integrating dissimilar materials. We will address future prospects of the new 2D/3D heterogeneous integrated circuits towards realizing future communication, computing, and imaging systems, and will discuss their impacts on future cyberinfrastructures.