Comparison of the ISM properties of a wide range of metal-poor galaxies with normal metal-rich galaxies reveals striking differences. We find that the combination of the low dust abundance and the active star formation results in a very porous ISM filled with hard photons, heating the dust in dwarf galaxies to overall higher temperatures than their metal-rich counterparts. This results in photodissociation of molecular clouds to greater depths, leaving relatively large PDR envelopes and difficult-to-detect CO cores. From detailed modeling of the low-metallicity ISM, we find significant fractions of CO-dark H2 - a reservoir of molecular gas not traced by CO, but present in the [CII] and [CI]-emitting envelopes. Self-consistent analyses of the neutral and ionized gas diagnostics along with the dust SED is the necessary way forward in uncovering the multiphase structure of galaxies