Abstract This paper analyzes the main sources of power consumption in Networks-on-Chip (NoC)-based systems. Analytical power models of global interconnection links are studied at different levels of abstraction. Additionally, power measurement experiments are performed for different types of routers. Based on this study, we propose a new topology-based methodology to optimize the power consumption of complex NoC-based systems at early design phases. The efficiency of the proposed methodology is verified through a case study of an MPEG4 video application. Experimental results show a promising improvement in power consumption (8.55%), average number of hops (10.80%), and number of global links (56.25%) compared to the best known related work.