A high throughput analysis of SAM MTase electrostatic and topological properties is needed to rationalize how this diverse class of enzymes has evolved to achieve a narrow distribution of kinetics albeit substrate diversity. Existing studies have used different types of MTases but remained relatively low throughput, usually using one or two structures. A notable exception is the structural survey conducted by the Trievel lab, which involves 46 different SAM MTases. Combined growth in computational resources and protein databank (PDB) entries makes a strong case for higher throughput studies that have greater potential to uncover more universal trends. Here, we present a computational analysis of 91 high-quality SAM MTase structures that examines both enzyme interior electric field (EF) strength and cavity volume using EnzyHTP, a high-throughput enzyme modeling software developed by our lab. Existing computational and experimental studies of SAM MTases 29 and other types of enzymes have elucidated interior enzyme electrostatics to be among the determining factors in mediating catalytic efficiency. Volume of active site cavity represents a topological factor that informs the capability of SAM MTases in substrate binding. Measuring both an electrostatic and topological value provides a holistic view of how each MTase has evolved to the specific characteristics of their respective substrates to achieve strong catalytic efficiency. Our analyses of 91 unique SAM MTases have enabled us to evaluate how SAM MTases have evolved to specific characteristics of their substrates' target atoms, the diversity of their class of target substrates, and the presence of metal ions in their structures.