In 1661 his superiors sent him, together with the Belgian Father Albert Dorville or d'Orville, to Rome in order to defend Schall's work on the Chinese calendar on the charge of having encouraged 'superstitious practices'.
As it was impossible to journey by sea on account of the blockade of Macau by the Dutch, they conceived the daring idea of going overland from Peking to Goa (India) by way of Tibet and Nepal.
Jesuit Father Heinrich Roth, a Sanskrit scholar, substituted for Dorville and with Grueber carried on the overland journey through Persia and Turkey, reaching Rome on the 2 February 1664.
Though in poor health Grueber lived another 14 years as preacher and spiritual guide in the Jesuit schools of Trnava (Slovakia) and Sárospatak (Hungary), in the latter of which he died on 30 September 1680.
An account of this first journey through Tibet in modern times by a European was published in 1667 by Athanasius Kircher to whom Grueber had left his journals and charts, which he had supplemented by numerous verbal and written additions.