Dusty star-forming galaxies (DSFGs) at high redshift play an important role in the stellar assembly of the early universe. These intensely star-forming galaxies with star formation rates (SFR) ranging from tens to thousands of solar masses per year are enshrouded in dust and bright in the far-infrared and sub-millimeter wavelengths. The physics of the interstellar medium can be studied through molecular observations. Molecular hydrogen (H2) is the fuel for star formation and can be traced by carbon monoxide (CO). Water (H2O), which is one of the most abundant molecules in the universe, is a good tracer of the infrared radiation. In my thesis talk, I will present a detailed analysis of molecular observations in the high redshift sub-millimeter galaxies (SMGs) discovered in the South Pole Telescope (SPT) survey. From the resolved H2O observations with ALMA, we find that the lower energy transitions of H2O are correlated with far-infrared luminosity on both global and kiloparsec scales within both starburst galaxies and an active galactic nuclei. This result suggests that H2O can be used as a resolved SFR indicator. I will also present a detailed molecular characterization of SPT0311-58 at z=6.9, which is just ~800 Myr after the Big Bang. It is the most massive infrared luminous galaxy pair discovered in the Epoch of Reionization (EoR) and the earliest detections of H2O in a starburst galaxy. I will present the results from the radiative transfer modeling of CO transitions, [CI], and dust in this early pair of galaxies. From our analysis, we find that SPT0311-58, in the EoR, is similar to other high-redshift SMGs.