Chilean air services are well-developed, but connecting the desert north with the humid south will always involve changing planes in Santiago [1]. Bus is the primary means of overland transport, but the passenger rail network reaches the southern mainland cities of Concepción [2] and Puerto Montt [3]. There is also commuter rail from Santiago south to San Fernando, and from Valparaíso [4] to nearby communities.
Links:
[1] http://www.moon.com/destinations/chile/santiago-and-vicinity
[2] http://www.moon.com/destinations/chile/-chilean-heartland/concepcion
[3] http://www.moon.com/destinations/chile/sur-chico/puerto-montt
[4] http://www.moon.com/destinations/chile/-chilean-heartland/valparaiso