Much of the southern part of the route runs through rural areas of Salem and Gloucester counties, passing through the communities of Woodstown and Mullica Hill.

The northern terminus of Route 45 was moved to its current location in 1953 in order to avoid the concurrency with US 130.

A freeway for Route 45 between I-295 in Woodbury and US 322 in Mullica Hill was recommended by the Delaware Valley Regional Planning Commission in the 1960s.

At the crossing of the latter, Route 45 enters Mannington Township and becomes an unnamed road that passes marshland with some development.

[1][2] Here, Route 45 turns to the east and forms a concurrency with CR 540, passing through farmland with some woods and homes.

[1] Here, the route intersects CR 679 near the Salem County Veterans Cemetery before heading through more agricultural areas.

[1] A short distance later, the route enters Pilesgrove Township again and heads back into farmland with some residences and forested areas as an unnamed road, crossing CR 660.

[1][2] Route 45 crosses Oldmans Creek into South Harrison Township, Gloucester County within woodland and continues through rural areas with some residential developments such as Woodstown-Mullica Hill Road.

ends and CR 536 turns west along US 322, and Route 45 continues northeast along Main Street, passing residential and commercial development as a state-maintained road.

[1][2] After the intersection with the latter, the route becomes a four-lane undivided road, entering Woodbury and immediately crossing the Southern Railroad of New Jersey's Salem Branch line at-grade.

[1] The road crosses Conrail Shared Assets Operations' (CSAO) Penns Grove Secondary railroad line at-grade before coming to an intersection with CR 551.

[1][2] The route widens into a four-lane divided highway as it comes to a partial interchange with I-295, with some of the movements provided by nearby CR 551 to the east.

[11] In the 1953 New Jersey state highway renumbering, the northern terminus of Route 45 was cut back to its current location in Westville to avoid the concurrency with US 130.

[12][13] In the late 1960s, the Delaware Valley Regional Planning Commission (DVRPC) proposed construction of a 10-mile (16 km) long, $20 million freeway along the Route 45 corridor in Gloucester County which would have extended from Exit 24 of I-295 in Woodbury to a planned US 322 freeway in Mullica Hill.

[16] The New Jersey Department of Transportation is planning on rebuilding Route 45 in Woodbury to make it more friendly to pedestrians and bicyclists.