Abstract: Systems and methods for demographic grouping are disclosed. In certain embodiments, the technology involves receiving a dataset comprised of one or more of omics, physiological, EMR and contextual data and minimizing a weighted sum multi-objective function at an optimizer through a multi-objective optimization process. A plurality of constraints, initial conditions and hyperparameters are applied to the objective function and optimization process to generate potential sub-population clusters. Then the potential sub-population clusters are compared through statistical and functional evaluation of differentially expressed genes and gene ontology resulting in the optimal solution for the targeted phenotype as the output.