SMOKE can accommodate a variety of chemical mechanisms for the models it supports. From the emissions processing perspective, the chemical mechanism is the mapping of the pollutants provided in the emissions inventory to the species needed by the AQM of interest. For example, the input files for five chemical mechanisms for the CMAQ model are available for download from the EPA; these mechanisms are Carbon Bond 6 (CB6), CB6 with particulates, Regional Acid Deposition Model, 2 (RADM2), RADM2 with particulates, and a research version of CB6 with toxics.

SMOKE users must know what chemical mechanism will be used in the AQM for which the SMOKE output emissions are intended. Once that has been determined, the following files must be configured to be consistent with the inventory being used and the chemical mechanism: the inventory table (INVTABLE), speciation profiles (GSPRO), speciation cross-reference (GSREF), and the mobile processes file (MEPROC) when creating on-road mobile emissions with MOVES through SMOKE.