The pair are set to be named in the starting line-up for the Hammers as they bid to maintain their fine start against Alan Pardew's men at St James' Park.
Nolan enjoyed three successful years with the North East club, helping them to the Championship title in 2010, before moving to Upton Park the following summer.
Local-boy Carroll meanwhile came through the Newcastle youth ranks before his record-breaking £35million move to Liverpool in January 2011.
Santon was quick to stress the team threat posed by an in-form West Ham side currently ninth in the table but did acknowledge that special attention will need to be paid to the former Magpies duo.
"West Ham will be a difficult game. They have some good players," he said. "They have Andy Carroll and Kevin Nolan, so we have to be careful.
"It is very important for us to win the game. We are only playing for a win.
"We have to stop them. We know they are coming here to score. However, we know we have a great defence here. We have a great team and we can stop them."
Pardew's side came close to qualifying for the Champions League last season, eventually ending a fine campaign in fifth place.
They have yet to hit the heights they reached last year so far this season, as they strive to juggle the demands of the Premier League and European football.
However, they are unbeaten in their last five matches and Santon insists a top four challenge is still their main aim this season.
"Last year, we had a really big chance to get there," added Santon. "We finished fifth in the end, but we have a very good team and have a good chance of getting there.
"We just have to get back into the winning mentality every game.
"We are in a great position to move forward."