The Caloosahatchee River is located on the southwest Gulf Coast of Florida, USA, and is approximately 67 miles (108 km) long. It drains rural areas on the northern edge of the Everglades, east of Fort Myers. The river serves as an important link in the Okeechobee Waterway, a manmade inland waterway system of southern Florida. The river forms a tidal estuary along most of its course and has become the subject of efforts to restore and preserve the Everglades.

The EFDC+ Caloosahatchee model domain comprises of 4,041 grid cells with an orthogonal deviation of 0.45. The average cell size is 370 m x 330 m. This grid was built for use with EFDC+ Explorer and Grid+.