“We need to behave naturally and not try to find an excuse, that’s never good,” said Pochettino, 44.
“It’s a chance to play on a big pitch.”
Spurs, who have started their season with two Premier League wins and two draws, will also entertain CSKA Moscow and Bayer Leverkusen in their Champions League group.
Striker Harry Kane believes the prospect of up to 90,000 Tottenham fans in the national stadium is “only going to make you play better”.
Arsenal’s move to Wembley for two Champions League campaigns in 1998 and 1999 delivered just two wins from six games.
Spurs, quarter-finalists in 2011, have two pitches at their training ground with the same dimensions as Wembley, a stadium they have won just once at since it was re-opened in 2007.
“You have more space to play, it’s more difficult for the opponent to press you when there are more metres to run,” added Pochettino, who has never managed in the Champions League.
“We trust in us. We feel good at White Hart Lane because it’s our home and we need to feel good at Wembley.”
Defender Danny Rose remains sidelined with a hamstring injury but Pochettino otherwise has a full squad to choose from against a side Tottenham played twice in last season’s Europa League, winning 4-1 and drawing 1-1.
Monaco will be without defender Benjamin Mendy but manager Leonardo Jardim has Radamel Falcao as a striking option as his side look for a sixth win in a row.
Jardim’s side – eliminated in Champions League qualifying last season – have three wins and a draw in Ligue 1, overcoming Paris St-Germain and Lille in the process.