Systems exposure science has emerged from the traditional environmental exposure assessment framework and incorporates new concepts that link sources of human exposure to internal dose and metabolic processes. Because many human environmental studies are designed for retrospective exposure evaluations they often do not provide practical toxicological outcome parameters. Our goal was to examine concepts from systems biology research and adapt them to a network approach that maps forward to a perturbation event using two hypothetical examples. The article proposes that environmental exposure studies should not only retrospectively document exposure levels, but also measure biological parameters that can be used to inform relevant systemic changes.