New manager Stephen Kenny is yet to taste victory since taking over from Mick McCarthy last summer and saw his side bow out of the Euro 2020 play-offs at the semi-final stage.
Here, the PA news agency takes a look at some of the talking points surrounding a testing trip to Belgrade.
Ninth time lucky?
Kenny was thrown straight in at the deep end as he presided over Nations League encounters with Bulgaria and Finland as a precursor to last October's Euro 2020 play-off semi-final trip to Slovakia, where his side were unfortunate to lose on penalties after a goalless draw. In all, his reign to date amounts to three draws and five defeats and while the odds may be against a first victory in Belgrade, a positive result would set his team up perfectly for Luxembourg's visit to the Aviva Stadium on Saturday.
Keeping it real
Darren Randolph's absence through injury handed Kenny a big decision, with talent and potential not in short supply but experience an extremely rare commodity. In the event, 21-year-old Bournemouth goalkeeper Mark Travers, who has two friendly appearances under his belt for the senior team, got the nod ahead of Kieran O'Hara and the uncapped Gavin Bazunu, and all eyes will be on him at the Rajko Mitic Stadium.
Seamus it ever was?
At the other end of the scale, Ireland could welcome back one of their stalwarts in Belgrade. Skipper Seamus Coleman last pulled on a green shirt in a Euro 2020 qualifying defeat in Switzerland 17 months ago with a combination of injuries and the competition for the right-back spot provided by Matt Doherty having hampered him since. Everton's 56-times-capped full-back has been a willing and able servant to his country for a decade and will hope for a chance to prove he still has a key role to play.
Time to strike
Kenny's wait for a win has been due largely to the fact that his team have scored just once during his time in charge, Shane Duffy's injury-time equaliser in Bulgaria. The four specialist frontmen in his squad have only 18 Ireland goals between them and 17 of those have been scored by Shane Long, who has not registered for his country since his strike in Moldova in October 2016. Callum Robinson has a friendly goal against New Zealand to his name, while Aaron Connolly and Troy Parrott are yet to open their accounts.
Back to the future?
Ireland have played only one competitive game in Serbia since the break-up of the former Yugoslavia, a 2-2 World Cup qualifying draw in September 2016. They got off to the perfect start when Branislav Ivanovic deflected Jeff Hendrick's shot into his own net, but trailed 2-1 thanks to Filip Kostic's strike and a Dusan Tadic penalty. However, Daryl Murphy snatched a point with his first senior international goal in his 24th appearance as the visitors rode their luck to emerge with tangible reward.