While the Wanderers dominated large parts of the contest, much like the derby in round three, Smeltz's late strike ensured the Sky Blues took all three points away from Wanderland.
It looked as though Dario Vidosic's sublime strike in the 58th minute, after some great lead up play from Romeo Castelen, would give the hosts a share of the points, after Jacques Faty's first-half opener.
But Sydney FC had other ideas and their win moves Graham Arnold's side up to third on the A-League table, level on points with the Wanderers.
The Sky Blues opened the scoring through Faty after a well-taken corner from Chris Naumoff, that was headed back into the danger area by Sebastian Ryall, and the Senegal defender leapt above Nikolai Topor-Stanley with a strong header to put the visitors in front.
The match threathened to erupt at times, particularly after Rhyan Grant's questionable challenge on Mitch Nichols right in front of the Sydney FC bench, just two minutes shy of the break.
Off the back of a capacity home crowd of 19,627, the Wanderers came out swinging and Vidosic came close to opening the scoring in the 8th minute, but he skewered his shot wide of goal.
Sydney FC appeared behind the eight ball from the outset, but they took the lead well against the run of play.
Nichols then almost brought the hosts level in the 36th minute, but he was thwarted by Sydney goalkeeper Vedran Janjetoic.
Vidosic looked like he'd taken a well deserved share of the spoils for his side, but Smeltz had other ideas.
Western Sydney Wanderers 1 (Vidosic 58') lost to Sydney FC 2 (Faty 22', Smeltz 90')