It is approximately 1.2 miles (1.9 km) long and flows through East Buffalo Township and Lewisburg.

It is very small and is not a perennial stream, but is impacted by stormwater flows and also has high concentrations of sediment.

Miller Run begins at the base of a small hill in East Buffalo Township.

In this reach, the stream crosses US Route 15, passes through the Bucknell University campus (where it receives an unnamed tributary from the left), and enters Lewisburg.

[2][3] The lower reaches of the stream lack a perennial flow during significant portions of the year, especially during droughts.

This is caused by large amounts of water flowing into it from storm drains and runoff-impervious surfaces.

[2] The average annual rate of precipitation in the watershed of Miller Run is 1.04 meters (3.4 ft).

[2] The surficial geology in much of the watershed of Miller Run consists of unconsolidated sediment from the Pleistocene period.

More recently, culverts, concrete channels, riprap, parking lots, and other developments by Bucknell University have further impacted it.

[2] There are a number of culverts on it between the Sunflower Daycare Center driveway and its confluence with Limestone Run.

[2] Miller Run has been described as "not appealing on the University campus" and can damage property during high flow conditions.

[5] In one reach, Miller Run flows past private property that was built on an old coal ash landfill.

[4] Miller Run has historically experienced significant modifications to increase its ability to carry away stormwater.

[2] Some time in or before 2011, a major research project involving 80 students and 11 faculty members was carried out on Miller Run.

The project involved GIS mapping, drone flights, sediment and water samples, and GPS measurements.

The project was an extension of studies done by Allison Shaffer in 2007 and a stream restoration course taught by Bucknell University professors Craig Kochel and Matt McTammany in 2009.

In 2010, the Pennsylvania Department of Environmental Protection awarded Bucknell University a $178,000 Growing Greener grant to restore the upper reaches of the stream.

[3] In 2015, a restoration project on the stream attracted some criticism from users of the golf course, as it has dried up the area and caused the driving range to look "like a desert" and business had been significantly reduced.

However, the Bucknell University website states that the project—which is supported by a $270,000 Growing Greener grant—"could change the way stream monitoring and restoration is carried out statewide".

[6] Miller Run is considered by the Pennsylvania Department of Environmental Protection to be a Warmwater Fishery.

Twenty individuals from six species—namely, bluegill sunfish, central stoneroller, creek chub, cutlips minnow, common shiner, and pumpkinseed sunfish—were observed in the upper reaches.

On a scale of 0 to 100, various sites on Miller Run had an IBI score of 14.47 to 25.82 (values below 63 indicate an impaired waterbody).

[2] Common macroinvertebrate taxa in Miller Run at site MR-1 include Diptera, Amphipoda, Turbellaria, and Isopoda.

The concentration of Chlorophyll a in Miller Run ranges from 2 to 12 micrograms per square centimetre (6.6×10−5 to 0.000393 oz/sq ft), and varies even at a single site.