Bernd Stange's men claimed a 2-1 win at Jalan Besar Stadium to move into third in Group A, two points adrift of second-placed Jordan.
The German's side are outsiders to qualify with Oman and Jordan among their competitors but another win over Syria would put some pressure on the top two.
Singapore had failed to score in the group before netting twice on October 15 through Khairul Amri and Gabriel Quak Jun Yi.
Syria are winless in 2013 and are without a victory over Singapore in their only previous two matches.
Due to security concerns, Hussam Al Sayed's men are playing home games in Iran and host Singapore at the Shahid Dastgerdi Stadium.
In their only group match at the venue so far, Syria held Jordan to a 1-1 draw and will be hoping for a similar result again.
Singapore named a youthful 20-man squad for the trip but one that is different to the side which won at home to Syria.
Stange has to deal with an entirely different back four, with Madhu Mohana (national service), Baihakki Khaizan (suspended) and Safuwan Baharudin and Shaiful Esah (both personal reasons) missing.
Tampines Rovers striker Amri, 28, provides plenty of experience up front and has scored 17 goals for his country.
A younger squad may find it difficult but Singapore desperately need a win if they are to qualify for Australia 2015.
