This review article takes a new look at the problem of characterization of structural properties and reaction dynamics of supported metal catalysts. Such catalysts exhibit an inherent complexity, particularly due to interactions with the support and the adsorbate molecules, which can be highly sensitive to environmental conditions such as pressure and temperature. Recent reports demonstrate that finite size effects such as negative thermal expansion and large bond length disorder are directly caused by these complex interactions. To uncover the atomistic features underlying the reaction mechanisms and kinetics of metal catalysts, experimental characterization must accommodate the challenging operation conditions of catalytic processes and provide insights into system attributes. The combined application of x-ray absorption spectroscopy (XAS) and transmission electron microscopy (TEM) for this type of investigations will be examined, and the individual strengths and limitations of these methods will be discussed. Furthermore, spatial and temporal heterogeneities that describe real catalytic systems and can hinder their investigation by either averaging (such as XAS) or local (such as TEM) techniques alone will be addressed by conjoined, multiscale, ab initio density functional theory/molecular dynamics modeling of metal catalysts that can both support and guide experimental studies. When taken together, a new analysis scheme emerges, in which different forms of structure and dynamics can be fully characterized by combining information obtained experimentally by in situ XAS and electron microscopy as well as theoretically via modeling. V