Constraint-based models enable the computation of feasible, optimal, and realized biological phenotypes from reaction network reconstructions and constraints on their operation. To date, stoichiometric reconstructions have largely focused on metabolism, resulting in genome-scale metabolic models (M-Models). Recent expansions in network content to encompass proteome synthesis have resulted in models of metabolism and protein expression (ME-Models). ME-Models advance the predictions possible with constraint-based models from network flux states to the spatially resolved molecular composition of a cell. Specifically, ME-Models enable the prediction of transcriptome and proteome allocation and limitations, and basal expression states and regulatory needs. Continued expansion in reconstruction content and constraints will result in an increasingly refined representation of cellular composition and behavior.