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design, both inter- and intra-chiplet, impacts overall system performance as well as its manufacturing cost and thermal feasibility. This paper introduces a cross-layer methodology for designing networks in 2.5D systems. We optimize the network design and chiplet placement jointly across logical, physical, and circuit layers to achieve an energy-efficient network, while maximizing system performance, minimizing manufacturing cost, and adhering to thermal constraints. In the logical layer, our co-optimization considers eight different network topologies. In the physical layer, we consider routing, microbump assignment, and microbump pitch constraints to account for the extra costs associated with microbump utilization in the inter-chiplet communication. In the circuit layer, we consider both passive and active links with five different link types, including a gas station link design. Using our cross-layer methodology results in more accurate determination of (superior) inter-chiplet network and 2.5D system designs compared to prior methods. Compared to 2D systems, our approach achieves 29% better performance with the same manufacturing cost, or 25% lower cost with the same performance.