Nancy O'Malley first came to the University of Kentucky in 1979 to conduct an archaeological survey of Fort Knox Military Reservation. She remained at UK as staff archaeologist of the Program for Cultural Resource Assessment (PCRA), the contract archaeology unit now known as Program for Archaeological Research (PAR) from 1980 to 2000; she also worked parttime for the Willliam S. Webb Museum of Anthropology until she was hired as fulltime Assistant Director in 2000. Nancy served on the committee that made possible the Historic Preservation Program in the College of Design and later taught a core graduate course in the program for ten years. She has co-taught UK archaeological field schools and often collaborates with Transylvania University Professor Christopher Begley in archaeological field schools held during the May session.

Nancy has conducted both prehistoric and historic archaeological research in Texas, Kansas, Kentucky, Tennessee and West Virginia but shifted her focus exclusively to historic archaeology after 1986. Among her many research interests are the historic settlement era of Kentucky, industrial archaeology (particularly early redware potteries and the milling industry), African-American archaeology and social class studies. She has given many conference papers, and published articles and book chapters on her research interests. Most recently, she co-authored a book entitled  Kentucky's Frontier Highway: Historical Landscapes along the Maysville Road with geographer Karl Raitz, published in 2012 by the University Press of Kentucky.