The two nations, currently ranked outside of the world's top 150, will be looking to avoid finishing bottom of their group for the very first time in their history.
Match preview
An encounter against San Marino is one of the only occasions when Andorra are considered the favourites to win a football match.
The Tricolours have only ever won seven games since joining FIFA in 1996, though one of those successes was a 2-0 friendly victory against San Marino in 2017, their only previous meeting against them.
Koldo Alvarez, a former goalkeeper who earned 78 caps for Andorra, has been the country's manager since 2010 and has overseen four of these victories, with the hope of securing a fifth on Thursday.
After scoring consolation goals against Hungary and the Republic of Ireland, before claiming a goalless draw at home to Gibraltar in their last fixture, Andorra have something which for them resembles a decent run of form heading into their midweek clash.
Only Anguilla (210th) are lower than San Marino (209th) in the current FIFA world rankings, and that is not surprising, considering they have lost 67 of their 69 World Cup qualifiers.
Thursday's encounter will not be a David versus Goliath fixture, however, and if they are to win their first ever competitive game, then clashes against Andorra are ones they will certainly look to target.
Although 2020 was a year to forget for many footballing clubs and countries, it turned out to be a relatively successful year for San Marino, who claimed two goalless draws in their final two matches of the Nations League, with their first against Lichtenstein ending a miserable 40-game losing run across all competitions.
Franco Varrella's side have finished bottom in each of their seven World Cup qualifying campaigns since being recognised as a footballing nation by FIFA in 1990, and they will need to claim points against the likes of Andorra if they are to climb from the foot of their group for the very first time.
Andorra World Cup Qualifying - Europe form:
Andorra form (all competitions):
San Marino World Cup Qualifying - Europe form:
San Marino form (all competitions):
Team News
Andorra tend to play with a five-man defence in an attempt to keep goals conceded at a minimum, and they will likely do so again on Thursday.
41-year-old captain Ildefons Lima made his 131st appearance as a substitute against Gibraltar - nearly 23 years after making his national team debut - and the veteran centre-back will be in contention to start alongside Max Llovera and Marc Vales.
San Marino, meanwhile, are set to stick with a back four, which could see Davide Simoncini return to the heart of the defence, having missed the last three international matches.
Striker Matteo Vitaioli - one of only three current squad members to have scored an international goal - is expected to lead the line alongside 35-year-old Adolfo Hirsch, who has yet to score for his country in 43 appearances.
Andorra possible starting lineup:
Gomes; San Nicolas, Vales, Lima, Llovera, Cervos; Martinez, Vieira, Rebes, Pujol; Alaez
San Marino possible starting lineup:
Benedettini; Palazzi, Brolli, Fabbri, Gandoni, Rossi; E. Golinucci, Tomassini, A. Golinucci; Vitaioli, Hirsch
We say: Andorra 1-0 San Marino
Andorra and San Marino have rarely headed into any fixture with real belief that they can claim a victory, though Thursday's match is certainly one that provides both nations with confidence of securing all three points.
A closely-fought contest is set to be played out at the Estadi Nacional, with few goals to be expected, but we can see the hosts securing a narrow win on home soil.