O'Neill's side travelled to the Ta'Qali National Stadium on the back of a disappointing World Cup qualifying draw with Azerbaijan and had hoped to pick up their first win under the former Shamrock Rovers boss.
However it was Malta who made the brighter start in Valletta as Andre Schembri forced a save out of Alan Mannus after just five minutes.
William Grigg squandered the best chance for Northern Ireland in the first half when he went through on goal thanks to a fine pass from Chris Brunt, but was let down by a poor first touch.
That set the tone for the rest of the game but Malta could have taken the lead on more than one occasion, as Schembri lashed another shot over the bar from 18-yards before Misfud saw a late chance superbly saved by Mannus.
Northern Ireland have now drawn their last four successive matches in all competitions and are eight games without a win under O'Neill since he took charge in December 2011.