As the complexity of applications grows with each new generation, so does the demand for computation power. To satisfy the computation demands at manageable power levels, we see a shift in the design paradigm from single processor systems to Multiprocessor Systems-on-Chip (MPSoCs). MPSoCs leverage the parallelism in applications to increase the performance at the same power levels. To further improve the computation to power consumption ratio, MPSoCs for embedded applications are heterogeneous and integrate cores that are specialized to perform the different functionalities of the application. With technology scaling, wire power consumption is increasing compared to logic, making communication as expensive as computation. Therefore customizing the interconnect is necessary to achieve energy efficiency. Designing an optimal application specific Network-on-Chip (NoC), that meets application demands, requires the exploration of a large design space. Automatic design and optimization of the NoC is required in order to achieve fast design closure, especially for heterogeneous MPSoCs. To continue to meet the computation requirements of future applications new technologies are emerging. Three dimensional integration promises to increase the number of transistors by stacking multiple silicon layers. This will lead to an increase in the number of cores of the MPSoCs resulting in increased communication demands. To compensate for the increase in the wire delay in new technology nodes as well as to reduce the power consumption further, multi-synchronous design is becoming popular. With multiple clock signals, different parts of the MPSoC can be clocked at different frequencies according to the current demands of the application and can even be shutdown when they are not used at all. This further complicates the design of the NoC.Many applications require different levels of guarantee from the NoC in order to perform their functionality correctly. As communication traffic patterns become more complex, the performance of the NoC can no longer be predicted statically. Therefore designing the interconnect network requires that such guarantees are provided during the dynamic operation of the system which includes the interaction with major subsystems (i.e., main memory) and not just the interconnect itself. In this thesis, I present novel methods to design application-specific NoCs that meet performance demands, under the constraints of new technologies. To provide different levels of Quality of Service, I integrate methods to estimate the NoC performance during the design phase of the interconnect topology. I present methods and architectures for NoCs to efficiently access memory systems, in order to achieve predictable operation of the systems from the point of view of the communication as well as the bottleneck target devices. Therefore the main contribution of the thesis is twofold: scientific as I propose new algorithms to perform topology synthesis and engineering by presenting extensive experiments and architectures for NoC design.