The design of state-of-the-art low-power wireless sensor nodes involves the convergence of many technologies and disciplines. Submicron complementary metal oxide semiconductor (CMOS) devices, micro-electro-mechanical system filters, on- and off-chip electromagnetic elements, sensors and thin-film batteries are some of the technologies that will enable pervasive systems such as wireless sensor networks. High system complexity requires the use of many simulation environment during design: algorithm simulators, mechanical finite element analysis, behavioural and transistor-level circuit simulators, electromagnetic (EM) simulators, thin-film battery simulators and network simulators. It is shown that highly integrated, self-contained systems require multiple-domain simulations to uncover complex interactions between domains. Specific examples of block- and system-level design methodologies used in low-power wireless systems are presented here. Bottlenecks in the current methodology will be identified with an eye towards improving the scope and resolution of system-level simulations.