Both nations are looking to rebuild after unsuccessful World Cup qualification campaigns, though Martin O'Neill will be without a number of regular first-team players
Drulovic has assumed temporary charge after Sinisa Mihajlovic resigned in November following Serbia's failure to qualify for this year's World Cup.
Serbia finished third in qualifying Group A after taking 14 points from their 10 games, with Croatia claiming the play-off place ahead of them.
A disappointing defeat to minnows Macedonia ultimately proved crucial in ending Serbia's hopes, but Drulovic will look to bring back some of the feel-good factor against an Ireland side who will also be watching the World Cup from home.
Drulovic rose to prominence when he guided Serbia's Under-19s to success at the 2013 European Championships in Lithuania, and the country's football association are hoping he can achieve similar things with the senior team - even if on a temporary basis.
"This is the best possible solution because Drulovic has earned his chance after achieving the historic success of winning the European Under-19 title last year," the Serbian Football Association said upon announcing Drulovic's appointment.
And the 45-year-old has already stamped his own mark on the side, recalling Roma midfielder Adem Ljajic to the national set-up after almost two years in the international wilderness after he was dropped by Mihajlovic for failing to sing the national anthem.
He is joined in the squad by Twente's Dusan Tadic, who represents a significant goal threat after netting 11 times in 25 Eredivisie matches so far this term.
For Ireland, the game also represents another phase in their own transition.
Their failure to qualify for the World Cup ended Giovanni Trapattoni's reign, although there have been encouraging early signs under new boss Martin O'Neill and his assistant Roy Keane.
Ireland are unbeaten in the two games that the pair have overseen - beating Latvia 3-0 and earning a creditable 0-0 draw with Poland.
Another positive result could give Ireland much-needed momentum ahead of what promises to be a difficult 2016 European Championship qualifying campaign.
O'Neill's side have been drawn alongside three-time European champions Germany in Group D, along with Poland, Scotland, Georgia and debutants Gibraltar.
Serbia's task is no less challenging, with Denmark, Portugal, Albania and Armenia also in Group I.
The two previous meetings between these sides have ended in draws, but O'Neill is set to be without a number of players through injury as Ireland aim to buck that trend.
Nottingham Forest midfielder Andy Reid misses out because of a groin injury, while Newcastle United goalkeeper Rob Elliot is unavailable due to a knee problem.
QPR striker Kevin Doyle also misses out, the 30-year-old having withdrawn from the squad with a thigh complaint.
Richard Dunne has also withdrawn, with the defender being rested by his club - although O'Neill insists he could still play a part in the qualifying campaign for the Euros.
"If the qualifying campaign (started) in the morning, because of the amount of games he has played and the form he has shown for Ireland over quite a number of matches, you would certainly have to give (his selection) consideration," said O’Neill, who called up QPR goalkeeper Brian Murphy on Monday.