Luckless fullback Trbojevic slipped over trying to catch a Joey Walsh pass midway through Sunday's first half and cut a dejected figure leaving the field at Cbus Super Stadium.
What initially appeared an innocuous fall could have major ramifications for the Sea Eagles, whose first season under Kieran Foran is losing steam at the worst possible time.
One win out of the top eight, ninth-placed Manly have lost four of their past five games and now face another stint without their frequently-injured talisman.
Trbojevic already missed eight weeks with an injury to his other hamstring earlier this year.
"Hopefully (it's) not as bad as the last one, but naturally he's pretty disappointed," Foran said.
"We'll wait until he gets a scan and then work out the damage."
Clayton Faulalo excelled as the Sea Eagles posted a 5-2 record without Trbojevic during his last hamstring lay-off.
But the back-up fullback is battling his own hamstring issue and won't return until at least round 23.
The Sea Eagles must claim victory in four of their remaining six games to finish with a winning record but have difficult clashes against Cronulla, Newcastle and the Warriors to come.
Rookie coach Foran led Manly into the top four within weeks of his mid-season appointment, but said he always knew there would be hurdles ahead.
"I didn't take the job thinking I wasn't going to be challenged. I love being challenged," Foran said.
"I've got full belief in where we're heading this year. I haven't deviated from that.
"We've just hit a bit of a flat spot in terms of not our energy and our intent ... but just the style of footy that we're playing is not helping us. We're self-inflicting a lot of pain."
Trbojevic's importance to Manly was reiterated as he and Jason Saab helped the visitors to a 10-0 lead inside six minutes on Sunday.
Saab tapped a Jamal Fogarty kick down for Trbojevic to score Manly's first, before the fullback threw the last pass for his right winger to score the first of his two tries.
Down eight points with 13 minutes to play, the Sea Eagles were given a golden chance to snatch the game back when the Titans lost winger Dean Ieremia to the sin bin for a hip-drop tackle.
But Manly were reduced to 12 men themselves after Josh Feledy committed a professional foul as the Sea Eagles were scrambling back following AJ Brimson's 70-metre tear.
In the next set, star fullback Keano Kini put Jojo Fifita in for a second try and made it a 12-point game in the last 10 minutes.
The 16th-placed Titans are no chance of playing finals but Josh Hannay's faith in his inexperienced players paid dividends in a fifth win of the year.
Rookie half Zane Harrison put Fifita into a hole ahead of the Queensland representative's first try before kicking through the line to help Brimson make it a 14-point game at the half.
Mature-age rookie Oliver Pascoe scored two tries in the game of his career and had a team-high 41 tackles at hooker.
Even so, the Titans missed 34 tackles, made 13 errors and conceded their second-biggest score in their past seven games.
"We won, but I would say that's nearly as bad as we've played all year. Just really loose," Hannay said.
"We're a lot better than what we were today."
