Evaluations of Listeria monocytogenes dose-response relationships are crucially important for risk assessment and risk management, but are complicated by considerable variability across population subgroups and L. monocytogenes strains. Despite difficulties associated with the collection of adequate data from outbreak investigations or sporadic cases, the limitations of currently available animal models, and the inability to conduct human volunteer studies, some of the available data now allow refinements of the well-established exponential L. monocytogenes dose response to more adequately represent extremely susceptible population subgroups and highly virulent L. monocytogenes strains. Here, a model incorporating adjustments for variability in L. monocytogenes strain virulence and host susceptibility was derived for 11 population subgroups with similar underlying comorbidities using data from multiple sources, including human surveillance and food survey data. In light of the unique inherent properties of L. monocytogenes dose response, a lognormal-Poisson dose-response model was chosen, and proved able to reconcile dose-response relationships developed based on surveillance data with outbreak data. This model was compared to a classical beta-Poisson dose-response model, which was insufficiently flexible for modeling the specific case of L. monocytogenes dose-response relationships, especially in outbreak situations. Overall, the modeling results suggest that most listeriosis cases are linked to the ingestion of food contaminated with medium to high concentrations of L. monocytogenes. While additional data are needed to refine the derived model and to better characterize and quantify the variability in L. monocytogenes strain virulence and individual host susceptibility, the framework derived here represents a promising approach to more adequately characterize the risk of listeriosis in highly susceptible population subgroups.