Enschede is at the end of a direct train line from Amsterdam via Utrecht and Amersfoort (roughly 2 hours). The train runs several times per hour during the day. From Amsterdam Schiphol Airport, direct trains run to Enschede via Amsterdam Centraal; the journey takes around 2.5 hours.
The nearest international airport is Enschede Airport Twente, which handles some budget flights (primarily Ryanair), though most visitors use Schiphol. By road, Enschede is on the A35 motorway, close to the German border — Münster in Germany is about 75 km away.