Spurs travel to Selhurst Park on Saturday lunchtime, which you can listen to live and exclusively on talkSPORT, and the north London side could be without a number of key men - including Heung-min Son.
The South Korean forward suffered a calf injury during his nation's match with Iraq during the international break, which saw him sit out the clash with Lebanon on Tuesday night.
The severity of his injury remains to be seen and, if they are without the 29-year-old, they will have to rely on the likes of Steven Bergwin and Lucas Moura.
Oliver Skipp and Ryan Sessegnon are also doubts for the game on Saturday after the duo picked up knocks whilst featuring for England Under-21s.
Skipp has started all of Spurs' first three league games so far this season and, despite a few shaky moments, has adapted to Premier League football relatively well.
However, the midfielder suffered a setback on Wednesday night after picking up a groin injury that forced him off during the Young Lions' win over Kosovo.
Harry Winks could come in for his compatriot and partner Pierre-Emile Hojbjerg and Dele Alli in midfield.
Sessegnon, who hasn't really been in Nuno's plans since the Portuguese took over, also suffered an injury blow while away with Lee Carsley's side.
The 21-year-old has had a poor record when it comes to injuries since joining the club from Fulham in 2019, and it looks almost certain that he will miss the trip to Palace.
A player who could be fit is Joe Rodon, who is yet to feature for Spurs this season. The Welsh defender suffered an injury in August which ruled him out of the start of the season, but linked up with his national team midway through the international break, prompting claims he could return.
His availability would be timely, as fellow centre-backs Cristian Romero and Davison Sanchez will definitely be missing in east London.
The duo were both in South America on international duty during the recent international break, represented Argentina and Colombia respectively, and as a result, they won't be able to link up with their Tottenham teammates for 10 days due to COVID-19 guidelines.
This could leave Spurs short on central defenders and could see Rodon return or see Japhet Tanganga play alongside Eric Dier, despite the youngster being used as a right-back so far this season.
This may mean that summer signing from Barcelona, Emerson Royal, is given his debut on the right-side of defence.
Midfielder Giovani Lo Celso will also miss the game, too, with the Argentine joining Romero and Sanchez in being amongst those caught up in the scenes as Argentina's match with Brazil was abandoned earlier this week.
All three are currently training in Croatia to see out their isolation period, with new boss Nuno confirmed they are due back at the club next Friday.
"I can tell you that they are in Croatia - that's what we decided to do to try to avoid more problems," the Tottenham manager told a press conference.
"So the solution was to try to get them in a country where, after that, they can join the group. Now they are working with the sports science, a physio, in Croatia.
"They will arrive the day before the match against Chelsea [on September 19].
The missing men does open up an opportunity for another new signing, Bryan Gil, to make his first Premier League start.
The Spanish winger could line-up in attack alongside Harry Kane, who has returned from England duty in good shape and good form after scoring a goals in each of the Three Lions' three games.