Santaní is about 230 km northeast of Asunción, roughly a four-hour drive depending on road conditions. The main route runs via Coronel Oviedo and then north through the San Pedro department on Route 3 (Ruta Mariscal Estigarribia). The road is paved to Santaní, which was not always the case — the improvement came in the 2000s and made a significant difference to the town's connectivity.
Buses run from the Asunción bus terminal (Terminal de Ómnibus) to Santaní several times daily. Several companies operate the route; expect the journey to take four to five hours. Shared taxis (taxis compartidos) sometimes make the run faster for a higher price. There is no train service to this part of Paraguay. If you are coming from the east (Ciudad del Este), you can connect through Coronel Oviedo, which is the regional hub for bus connections through central and northern Paraguay.