Spurs failed to persuade the former Chelsea boss to take the role last summer but now, with Santo axed after just four months, they have gone back for the Italian.
There is growing optimism at Tottenham that this time they will strike a deal.
Tottenham have returned to Antonio Conte with a fresh approach to become manager.
Tottenham made their move on Sunday night, hours before sacking Nuno Espirito Santo
It was just last week that Conte was being linked with replacing Ole Gunnar Solskjaer at Manchester United but after the Red Devils recorded an emphatic 3-0 win over Spurs, it is London where the 52-year-old could be heading.
Conte has been out of work since departing Inter Milan at the end of last season, leaving the San Siro after winning Serie A with the Italian giants for the first time since 2010.
At Tottenham’s London rivals Chelsea, Conte won the Premier League in 2017 – his first season at Stamford Bridge.
The following year, he won the FA Cup but was axed by Roman Abramovich with the club finishing fifth in the table.
Conte would be tasked with getting Tottenham playing more adventurous football than was seen under Santo and his predecessor, Jose Mourinho.
In his last position, Conte delivered Serie A glory to Inter Milan for the first time since 2010
Conte won the Premier League title back in 2017 when he was manager of Chelsea
Spurs chairman Daniel Levy (bottom right) was alarmed by the team’s Manchester United loss
Fans have felt disenchanted by the style of play under both Portuguese coaches and the Tottenham board were rattled at the anger from supporters in the aftermath of the United defeat.
Tottenham are eighth in the Premier League table after Santo’s 10 games in charge and are five points outside of the top four.
They meet Dutch side Vitesse Arnhem in the Europa Conference League on Thursday before returning to Premier League action away to Rafa Benitez’s Everton side on Sunday afternoon.