Mack works at the intersection between fundamental physics and astrophysics. Her research considers dark matter, vacuum decay, the formation of galaxies, observable tracers of cosmic evolution, and the Epoch of Reionization. Mack has described dark matter as "one of science's most pressing enigmas". She has worked on dark matter self-annihilation and has investigated whether the accretion of dark matter could result in the growth of primordial black holes (PBHs). She has worked on the impact of PBHs on the cosmic microwave background. She has become increasingly interested, too, in the end of the universe.