Nepomuceno is a second name and surname, meaning "of Nepomuk". Notable people with the surname include:
- Alberto Nepomuceno (1864–1920), Brazilian composer and conductor
- Daniel Nepomuceno Navarro (born 1991), American soccer player
- David Nepomuceno (1900–1939), Filipino sprinter
- Gevaro Nepomuceno (born 1992), Curaçaoan footballer
- Giovanni Nepomuceno Della Croce (1736–1819), Italian painter
- José Nepomuceno (1893–1959), Filipino film directors and producer
- Juan Nepomuceno Álvarez (1790–1867), Former president of Mexico
- Juan Nepomuceno Fernández Lindo (1790–1857), Honduran politician
- Juan Nepomuceno Guerra (1915-2001), Mexican drug lord
- Juan Nepomuceno Machado, Filipino-born Mexican merchant
- Juan Nepomuceno Rencoret (1856-?), Chilean doctor
- Juan Nepomuceno de Quesada (1738–1798), Spanish military officer
- Juan Nepomuceno Solá (1751–1819), Argentine Catholic priest
- Juan Nepomuceno Zegrí Moreno (1831–1905), Spanish Roman Catholic priest
- Pablo Diego José Francisco de Paula Juan Nepomuceno María de los Remedios Cipriano de la Santísima Trinidad Ruiz y Picasso (1881-1973), Spanish artist
- Paeng Nepomuceno (born 1957), Filipino bowler and coach
- Willie Nepomuceno, Filipino satirist and public intellectual