Frank was a member of the Nesser Brothers, a group consisting of seven brothers who made-up the most famous football family in the United States from 1907 until the mid-1920s.
Nesser frequently engaged in kicking contests with the legendary Jim Thorpe; he once was credited with a 63-yard field goal and his punts were recalled as averaging 70 yards in the air. Frank was also a sensational runner, but his greatest value for the Panhandles was as a passer. He led the Panhandles in scoring during most of his professional seasons.
Nesser was also a minor league baseball player in the Ohio State League from 1910–1914. He later played in the North Carolina State League in 1915 and 1916. After abandoning baseball for a few years he restarted his career in the Illinois–Indiana–Iowa League in 1920 and played one final season, in 1921, in the Michigan–Ontario League. He left baseball after 9 seasons in which he posted a .325 batting average.
