The terrestrial Ionosphere Thermosphere and Mesosphere (ITM) system is at the interface between interplanetary and lower-atmospheric processes and plays a uniquely important role in the solar-terrestrial system. The NASA Thermosphere, Ionosphere, Mesosphere, Energetics and Dynamics (TIMED) mission is dedicated to the study of the basic structure of this interface region, its spatial and temporal variability and processes responsible for this variability. For the past seven years TIMED and its four remote sensing instruments have transformed our understanding of this gateway region of near-Earth space by successfully characterizing the dynamics, energetics, thermal, and composition structures. TIMED, together with its groundbased partners and other domestic and international space programs, has allowed the Heliophysics research community to observe new aspects of the cause-and-effect chains linking the Sun, heliosphere, and magnetosphere to the Earth.s upper and lower atmospheres. The approved extension of TIMED operations through 2012 would also provide an observational record spanning an 11-year solar cycle and enable a quantitative understanding of the external and internal forces that drive the ITM system, including the anthropogenic lower atmospheric climate change. In this paper, we will present highlights of TIMED observational results, assess our current state of knowledge, and discuss issues related to on-going and future system science studies, especially in the context of gaining quantitative understanding of sources of atmosphere variability and predictive capability of long-term climate change in the ITM system.