Regular striker Kyle Lafferty is suspended for the next World Cup qualifier against Russia in March so has been left out of the squad for the friendly at the Ta'Qali National Stadium on February 6. Inverness are providing the sternest challenge to Celtic in the Clydesdale Bank Scottish Premier League and McKay is the division's leading goalscorer.
The 24-year-old is now in line to win his first senior cap, and O'Neill said: "Kyle has started all the qualifying games so we have to look at our options. Billy has been very good for Inverness this season, he's scored 20 goals. They're riding high in the SPL and we're delighted with the form he's in. I'm keen to get him involved. There's an opportunity there for all of the lads."
This is a first call-up for the 23-year-old, and O'Neill said: "He's having a very good season at Tranmere. They're having a great season, top of League One, and I've had people watching him in recent weeks. He's a player with a lot to offer and it's the right time to bring him in."
The other uncapped player in the 23-man party is 18-year-old Liverpool midfielder Ryan McLoughlin.
"We have to build a squad from our own players," said O'Neill.
"Ryan is an Under-19 player but he's showed up very well when he's come into the senior squad. He's got a lot of potential and great character and this is all part of his development."
Former Shamrock Rovers boss O'Neill has yet to win a match since taking charge of Northern Ireland 13 months ago, with the team having drawn three of their four World Cup qualifiers so far, including against Portugal.
Malta, who are without a point in their own qualifying campaign, should provide a good opportunity for O'Neill to break his duck.