Thermodynamic modelling of organic synthesis has largely been focused on deep-sea hydrothermal systems. When seawater mixes with hydrothermal fluids, redox gradients are established that serve as potential energy sources for the formation of organic compounds and biomolecules from inorganic starting materials. This energetic drive, which varies substantially depending on the type of host rock, is present and available both for abiotic (outside the cell) and biotic (inside the cell) processes. Here, we review and interpret a library of theoretical studies that target organic synthesis energetics. The biogeochemical scenarios evaluated include those in present-day hydrothermal systems and in putative early Earth environments. It is consistently and repeatedly shown in these studies that the formation of relatively simple organic compounds and biomolecules can be energy-yielding (exergonic) at conditions that occur in hydrothermal systems. Expanding on our ability to calculate biomass synthesis energetics, we also present here a new approach for estimating the energetics of polymerization reactions, specifically those associated with polypeptide formation from the requisite amino acids.