The objective of the proposed research is the electro-thermal co-design of interconnects and microfluidic cooling technologies to address the challenges of 2.5D and 3D heterogeneous integration in high-performance and quantum computing applications. Two key enabling technologies for such integration are (1) high-density interconnects and (2) effective thermal management solutions, both becoming increasingly critical as system architectures grow in complexity. This study proposes co-designing interconnect and microfluidic cooling technologies to simultaneously meet performance and reliability requirements in advanced packaging platforms. First, we investigate (1) system-level thermal management strategy for a 2.5D high-bandwidth memory (HBM) - graphic processing units (GPUs) integrated with top-side single-phase microfluidic cooling solution, designed to mitigate the challenges associated with multi-die, multi-height configurations and the increasing power density of the dies. Furthermore, as top-side microfluidic cooling technologies approach their limits, we delve into (2) inter-tier microfluidic cooling design for 3D-ICs where TSVs are integrated within a micropin-fin heat sink to enable efficient heat dissipation across stacked dies while maintaining electrical interconnection. Furthermore, we analyze(3) 3D copper compressible microinterconnects (CMIs) as an off-chip interconnect for advanced packaging and explore their potential extension to quantum packaging applications. Building on this preliminary study, the research proposes (1) topology-optimized interlayer cooling with localized TSV architectures to achieve higher bandwidth density while minimizing system temperature, and (2) single- or bi-layer CMIs as off-chip interconnects for quantum computing applications, with a focus on thermal and superconducting CMI technologies.