Guardiola surprisingly opted to start Gabriel Jesus and Riyad Mahrez in Manchester City’s opening game of the season against West Ham last weekend.
Club record scorer Sergio Aguero and last season’s player of the year Bernardo Silva dropped to the bench as the Citizens dominated the Hammers in a 5-0 thrashing.
A hat-trick from Raheem Sterling and goals from Jesus and Aguero put the champions top of the table on the opening weekend.
However, despite such a dominant win, the game against Tottenham could see both Aguero and Bernardo return to the starting line-up, with Jesus and Mahrez dropping to the bench.
New signing Joao Cancelo was an unused substitute against West Ham and is unlikely to start once again having only recently linked up with his new club.
This means Kyle Walker will retain his spot at right-back while a long-term knee injury to Benjamin Mendy means Oleksandr Zinchenko will start the game at left-back.
Record signing Rodri made his City debut in their last game and, with fellow holding midfielder Fernandinho lacking in match fitness, the Spaniard is likely to make his second start against Spurs.
German winger Leroy Sane will be out of action for up to seven months with an ACL injury.
Portuguese midfielder Bernardo will likely replace Mahrez on the right, with Guardiola revealing the 25-year-old was only benched against West Ham as an injury precaution.
“Bernardo had done nothing wrong,” Guardiola said, “but there was some little muscular problems.”
The decision of which striker to start, however, will be the most difficult.
Both Aguero and Jesus have scored 22 goals and provided six assists for club and country in 2019, proving just how little there is to separate the two.
However, Guardiola may just opt for the Argentinian Aguero because of his outstanding goalscoring record against Spurs.
The 31-year-old has netted 11 times and set up four goals in his 16 games against last season’s beaten Champions League finalists.
No matter who the City boss opts for, they are likely to cause Spurs trouble with both sides looking to make an early statement in their pursuit of the Premier League title.
Manchester City predicted line-up vs Tottenham – Premier League
Ederson; Walker, Stones, Laporte, Zinchenko; Rodri, De Bruyne, David Silva; Bernardo, Aguero, Sterling