The headwaters of the Nepean River form about 100 kilometres south of Sydney. The river flows north in remote water catchment areas and into Nepean Dam which supplies water for Sydney.
North of the dam, the river follows the western edge of Sydneys metrapolitan area, flowing past the towns of Camden, Wallacia and Penrith.
Warragamba River, Glenbrook Creek and Grose River feed into the Nepean before it becomes the Hawkesbury River below the Grose.

The river is known mostly as a summer bass fishery, carp, eel, Macquarie Perch (totally protected), eel tailed catfish, the odd silver perch, trout (folowing floods) and some estuary species are present in the lower reaches.

The best bass fishing is typically at dusk and dawn or immediately following heavy rain or during minor flooding (never enter flood waters).
Bass fishing with surface lures, spinner baits and hard body lures is popular with spin anglers.
Fly fishing with large dry flies such as surface poppers, grass hoppers and christmas beetles is very popular particularly at dusk and following heavy rain. Streamers and nymphs are preferred during the middle of the day when the fish are less active near the surface.