His reign was eventually terminated by the Ottoman invasion following the disintegration of Safavid Persia, which forced Vakhtang into exile in the Russian Empire.

During these years, he launched a series of long-needed reforms, revived economy and culture, reorganised administration and attempted to fortify the central royal authority.

During the years of captivity, Vakhtang requested aid from the Christian monarchs of Europe, particularly he sent his uncle and tutor, Sulkhan-Saba Orbeliani, on a mission to Louis XIV of France.

Later, in his last letters to the Pope Innocent XIII and Charles VI dated 29 November 1722, Vakhtang said that he had for years been secretly Catholic, but he could not confess it publicly "because of betraying people about me", and confirmed with it the reports of Capuchin missionaries from Persia.

[2] Assisted by the ruler of neighboring Kakheti as well as the beglarbeg of Shirvan, Vakhtang made significant progress in putting a halt to the Lezgins.

[2] The order, which came after grand vizier Fath-Ali Khan Daghestani's fall, was made by the instigation of the eunuch faction within the royal court, having persuaded the shah that a successful end of the campaign for Vakhtang would do the Safavid realm more harm than good; it would enable Vakhtang, the Safavid wali to form an alliance with Russia with the aim to conquer Iran.

After several delays, Peter himself led an army of about 25,000 and a substantial fleet along the west coast of the Caspian Sea in July 1722, initiating the Russo-Persian War (1722–1723).

Peter's promises to provide military support to the Caucasian Christians for final emancipation from the Persian yoke created a great euphoria among the Georgians and Armenians.

He directed his armies to seize territories along the Caspian, but chose not to confront the Ottomans who were already preparing to claim succession to Safavid rule in the Caucasus.

Vakhtang fled to Inner Kartli, From there he attempted to win support from the advancing Ottoman forces and submitted to the authority of the Sultan; but the Turks, having occupied the country, gave the throne to his brother Jesse, who again became a nominal Muslim.

Tsarina Anna consented to Vakhtang's project, but gave him instructions how to act in Persia, and in what manner he should induce the Georgians and Caucasian highlanders to become Russian vassals, and bring about their entire submission to Russia.

Among the books published in "Vakhtang's Printing Press" in Tbilisi was the 12th-century national epic poem The Knight in the Panther's Skin (Vep’khistkaosani) by Shota Rustaveli, accompanied by scholarly commentaries by the king himself.

[5] Vakhtang also chaired a special commission convened to edit and compile the corpus of Georgian chronicles covering the period from the Dark Ages to the early modern era.