ModelMuse is a graphical user interface (GUI) for the U.S. Geological Survey (USGS) models MODFLOW 6, MODFLOW–2005, MODFLOW-LGR, MODFLOW-LGR2, MODFLOW-NWT, MODFLOW-CFP, MODFLOW-OWHM, MODPATH versions 5, 6, and 7, ZONEBUDGET, PHAST, SUTRA 2.2, SUTRA 3.0, MT3D-USGS, and WellFootprint and the non-USGS model MT3DMS. This software package provides a GUI for creating the flow and transport input file for PHAST and the input files for the other models. ModelMuse supports parameter estimation with UCODE in MODFLOW–2005 and MODFLOW-NWT models and with PEST in MODFLOW and SUTRA models except for MODFLOW-LGR models. In ModelMuse, the spatial data for the model are independent of the grid or mesh, and the temporal data are independent of the stress periods. Being able to input these data independently allows the user to redefine the spatial and temporal discretization at will. This report describes the basic concepts required to work with ModelMuse. These basic concepts include the model grid, data sets, formulas, objects, the method used to assign values to data sets, and model features. The ModelMuse main window has a top, front, and side view of the model that can be used for editing the model, and a 3–D view of the model that can be used to display properties of the model. The side view is hidden for SUTRA models and for MODFLOW 6 models that use discretization by vertices (DISV). Only the top view is visible for WellFootprint projects. ModelMuse has tools to generate and edit the model grid or mesh. It also has a variety of interpolation methods and geographic functions that can be used to help define the spatial variability of the model. ModelMuse can be used to execute the models and can also display the results of all the models except PHAST and ZONEBUDGET. Examples of using ModelMuse with MODFLOW, SUTRA, WellFootprint, and PEST are included in the reports. on various ModelMuse releases. Additional examples are described in the help system for ModelMuse, which can be accessed from the Help menu. ModelMuse works with two types of spatial discretization in MODFLOW 6: structured grids (DIS) and discretization by vertices (DISV). Quadtree refinement is used to generate a DISV model from a structured-grid model. The locations and weights for ghost nodes used to improve DISV model accuracy are computed automatically by ModelMuse using a new algorithm. ModelMuse does not support other types of DISV grids and unstructured grids. ModelMuse supports options in MODFLOW 6 that designate individual cells as confined or convertible and remove inactive cells associated with discontinuous layers, thereby reducing the computational burden. ModelMuse can specify fully three-dimensional (3D), spatially variable anisotropy in hydraulic conductivity. Although MODFLOW 6 does not support the parameters supported by MODFLOW–2005, ModelMuse provides backward compatibility by allowing ModelMuse parameters to specify scale-factor variables in MODFLOW 6 time-series files within packages that support time-series files. ModelMuse can automatically convert the data for many of the packages from other MODFLOW models to the new data for these packages in MODFLOW 6. Some packages, such as the Streamflow Routing (SFR) package, changed significantly enough that only a partial conversion is possible. Head and flow observations in older models are also converted to observation locations in the MODFLOW 6 Observation Utility. ModelMuse accommodates the ability of MODFLOW 6 to store specific discharge components by allowing the user to visualize the components of a specific discharge on the model grid. ModelMuse supports the versions of MODPATH and ZONEBUDGET compatible with MODFLOW 6. ModelMuse can generate the input files for PEST when used with MODFLOW or SUTRA models, run PEST, and view the updated model inputs after parameter estimation with PEST. After a parameter has been defined in ModelMuse, it can be applied to all or part of a model data set. Pilot points can be used to assign spatially variable distributions of model inputs. Parameters can be applied to temporally varying features such as boundary conditions either by applying them to all the values in a series in one step or by applying separate parameters to individual members of a series. ModelMuse allows the definitions of many different sorts of observations from a variety of model output files. For MODFLOW 6 and SUTRA models, new options were added to ModelMuse to allow it to display the changed input after parameter estimation is complete. For MODFLOW-2005 and MODFLOW-NWT models, ModelMuse can import an entire model to allow it to be visualized.