The problem of quarkonium production in heavy ion collisions presents a set of unique theoretical challenges -from the relevant production mechanism of J/ψ and Υ to the relative significance of distinct cold and hot nuclear matter effects in the observed attenuation of quarkonia. In these proceedings we summarize recent work on the generalization of non-relativistic Quantum Chromodynamics (NRQCD) to include off-shell gluon (Glauber/Coulomb) interactions in strongly interacting matter. This new effective theory provides for the first time a universal microscopic description of the in-medium interaction of heavy quarkonia, consistently applicable to a range of phases such as cold nuclear matter, dense hadron gas, and quark-gluon plasma. It is an important step forward in understanding the common trends in proton-nucleus and nucleus-nucleus data on quarkonium suppression. We derive explicitly the leading and sub-leading interaction terms in the Lagrangian and show the connection of the leading result to existing phenomenology.