The Serie A club moved after the Romanian centre-back asked to leave in search of regular football, with Spurs' recent defensive signings only adding to the squeeze on his game time.
Terms are still being finalised, but the deal is expected to be structured as a loan carrying a £1million fee, followed by a permanent transfer valued at £15million.
Spurs have also secured a ten per cent sell-on clause covering any future profit Fiorentina make from reselling the defender.
A medical is pencilled in for Dragusin next week.
The 24-year-old arrived in north London from Genoa in January 2024, having turned down a late approach from Bayern Munich to try his luck in the Premier League instead.
Regular football proved elusive at Tottenham, and a serious knee injury only compounded his struggles for game time.
With Marcos Senesi and Jan Paul van Hecke both arriving at centre-back this summer, Dragusin's path to regular minutes under Roberto De Zerbi had narrowed considerably.
Fiorentina's sporting director Fabio Paratici, the man who first signed Dragusin for Tottenham, is understood to have driven the move to bring him back to Italy.
The switch marks a return to Serie A, where Dragusin previously excelled before making the jump to English football.
Tottenham have been active on both sides of the ledger this summer as they continue reshaping the squad under De Zerbi.
Dragusin's exit follows the departures of Luka Vuskovic and Alejo Veliz, helping Spurs offset a heavy summer of spending on new arrivals.
For Dragusin, the move offers a fresh platform in a league where he has previously proven his quality, and a chance to rebuild momentum after a difficult campaign.
Several other Serie A clubs had also shown interest in the defender, but Fiorentina's existing relationship with the player, forged through Paratici's Tottenham connection, ultimately proved decisive.
Dragusin's tenure in England had been complicated from the outset, with his physical style of defending never quite meshing with successive tactical setups at the club.
The knee problem that sidelined him for a significant stretch last season only added to his difficulties in nailing down a consistent run of starts.
For Tottenham, the deal represents another piece of business in what has already become one of the busiest transfer windows in the club's recent history, as De Zerbi continues to reshape his squad in his own image.