System-level electromagnetic design problems are multiscale and very challenging to solve. They remain a significant barrier to system design optimization for a foreseeable future. Such multiscale problems often contain three electrical scales, i.e., the fine scale (geometrical feature size much smaller than a wavelength), the coarse scale (geometrical feature size greater than a wavelength), and the intermediate scale between the two extremes. Existing commercial tools are based on single methodologies (such as finite element method or finite-difference time-domain method), and are unable to solve large multiscale problems. For example, no commercial software package is known to be able to model a simple package (say at 0.1 mm resolution) inside a reverberation chamber (1 m) for RF interference testing. We will present our recent work in solving realistic multiscale system-level EM design simulation problems in both frequency domain and time domain. In frequency domain, we combine the spectral element method for coarse scales and finite element method for fine scales with a fast spectral integral method. In time domain, we hybridize the spectral element time-domain method and finite-element time-domain method together with the perfectly matched layer, with explicit and implicit time integration schemes for different subdomains. The discontinuous Galerkin method is used as the subdomain interface condition. In time domain, we further incorporate a nonlinear circuit solver, making it possible to perform nonlinear circuit simulation with RF interactions in a seamless manner. Several previously intractable multiscale problems will be illustrated.