The US Environmental Protection Agency (USEPA) has a long history of leveraging environmental models and integrated modeling frameworks to support the regulatory development of numeric ambient water quality criteria for the protection of aquatic life and human health. Primary modeling types include conceptual, mechanistic, and data-driven empirical models; Bayesian and probabilistic models; and risk-based modeling frameworks. These models and modeling frameworks differ in their applicability to and suitability for various water quality criteria objectives. They require varying knowledge of system processes and stressor-response relationships, data availability, and expertise of stakeholders. In addition, models can be distinguished by their ability to characterize variability and uncertainty. In this work, we review USEPA recommendations for model use in existing regulatory frameworks, technical support documents, and peer-reviewed literature. We characterize key attributes, identify knowledge gaps and opportunities for future research, and highlight where renewed USEPA guidance is needed to promote the development and use of models in numeric criteria derivation. These outcomes then inform a decision-based framework for determining model suitability under particular scenarios of available knowledge, data, and access to technical resources.