Scott McTominay’s withdrawal through illness opens up a place at the right-hand side of Steve Clarke’s back three, where Souttar has excelled all season.
And with Lyndon Dykes and Ryan Christie are both suspended, Nisbet has an outside chance of being picked alongside Che Adams in attack.
It is Scotland’s penultimate game in Group F of the World Cup European qualifiers. Denmark have already won the group but Scotland are in a strong position to seal second spot.
Here we look at five talking points ahead of the game in Chisinau.
Scotland will secure second spot in the group and a place in March's play-off competition if they win. There will be other chances if they cannot get three points. Israel need to get a result in Austria later on and Scotland host Denmark on Monday. But Steve Clarke's men will be determined to wrap up the runners-up spot before facing the runaway leaders. Moldova are the weakest team in the group with only one point from eight games and lost to the Faroe Islands, so Clarke is likely to play an attack-minded team to get the job done.
Will Nisbet play?
Clarke will have to make at least five changes to the starting line-up that won in the Faroe Islands last month with two places up front needing cover. Lyndon Dykes, who has scored in the past four games, and Ryan Christie are both suspended. Che Adams, squad newcomer Jacob Brown and Hibs frontman Nisbet are vying for a strike role while the likes of John McGinn, David Turnbull and Stuart Armstrong could take up a role just off the front. Nisbet admits himself that he is not in good form, with only one goal since August, but he is a good option to have on the bench.
Will Souttar play?
Scott McTominay was sent home with a throat infection to leave Clarke without another defender after Grant Hanley pulled out with a groin injury. The good news is that Kieran Tierney is fit again after an ankle injury. Jack Hendry is likely to feature again leaving Liam Cooper of Leeds and Souttar battling for a place in the back three. Cooper has been steady for Leeds in the Premier League this season and never lets Scotland down. However, he is left footed and prefers to play in the middle of a back three. Souttar is better suited to the right centre-back role vacated by McTominay. His distribution and ability to step out of defence mean he has a chance.
Warning from history
Scotland drew 1-1 in Chisinau in October 2004 in a result that cost Berti Vogts his job as manager. Steven Thompson levelled soon after the hosts took a 28th-minute lead but Scotland suffered another major blow in their quest to reach the 2006 World Cup, having taken one point from their first two home matches.
Five in a row?
Scotland are looking to make it five consecutive victories for the second time in two seasons. They achieved the same feat when beating Serbia in the Euro 2020 play-off finals a year ago. That could be a good omen.