San Juan Nepomuceno is the department's liveliest town and a practical base for exploring eastern Caazapá: Caazapá National Park, Tavaí and its cenote, or Tres Kandú from the General Garay side. Its heart is Ykua Kurusu, the spring that marked the site of the town's founding, reached by the stairway of the Paseo de los Nepomucenos; at night, with the parish church lit up, is the best time for a stroll. In summer, the Capiibary stream is where locals cool off, and the town's shops draw buyers from all over the area.

Governor Lázaro de Rivera founded the settlement on November 20, 1797, and placed it under the patronage of St. John of Nepomuk, a Bohemian saint. Today it is the department's most populous district (28,233 residents in the 2022 census) and a hub for farming, ranching and forestry. Its patron-saint feast, May 14–16, keeps alive processions, torín (a playful mock bullfight) and traditional equestrian games such as the ring race, where riders spear a small ring at a gallop.