Like many of Hawaiʻi's neighborhoods, Mānoa consists of an entire valley, running from Mānoa Falls at the mauka (inland-most) end to King Street. The valley receives almost daily rain, even during the dry season, and is thus richly vegetated – though the valley walls are often dry. Seeing rainbows in the valley is a common occurrence, and is the source of the University of Hawaiʻi at Mānoa sports team names, the Rainbow Warriors and Rainbow Wahine.

The neighborhood is composed of private houses built before the 1960s and low-rise condominiums. Mānoa is home to the University of Hawaiʻi at Mānoa, the flagship campus of the University of Hawaiʻi System. The University has several faculty and student residence areas in Mānoa.

Mānoa is the site of the first sugarcane and coffee plantations in the Hawaiian Islands. John Wilkinson tended the first crops in 1825, brought on the ship HMS Blonde. Hawaiʻi is the only state that produces coffee commercially in the United States.