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New technologies for manufacturing 3D Stacked ICs offer numerous opportunities for the design of complex and efficient embedded systems. But these technologies also introduce many design options at system/chip design level, hard to grasp during the complete design cycle. Because of the sequential nature of current design practices, designers are often forced to introduce design margins to meet required specifications, resulting in sub-optimal designs. In this paper we introduce new design methodology and practical tool chain, called PathFinding Flow, that can help designers to easily trade-off between different system level design choices, physical design and/or technology options and understand their impact on typical design parameters such as cost, performance and power. Proposed methodology and the tool chain will be demonstrated on a practical case study, involving fairly complex Multi-Processor System-on-Chip using Network-on-Chip for communication medium. With this example we will show how High-Level Synthesis can be used to quickly move from high-level to RTL models, necessary for accurate physical prototyping for both computation and communication. We will also show how the possibility of design iteration, through the mechanism of feedback based on physical information from physical prototyping, can improve design performance. Finally, we will show how we can move in no time from traditional 2D to 3D design and how we can measure benefits of such design choice.