Manly eventually ran out 34-24 winners in Gosford, with Lehi Hopoate impressing in attack and young winger Navren Willett scoring a double.
New Rabbitohs halfback Lewis Dodd had little chance to impress in his first stint on the field, while the Wayne Bennett era kicked off with few of his regular players on the field.
Sea Eagles forward Taniela Paseka suffered a suspected low-grade shoulder injury in the win, while Souths utility Siliva Havili ended the match with a concussion.
The match was slated to start at 3.30pm AEDT but, with no paramedic on site at Central Coast Stadium, it became doubtful whether it would get underway at all.
A medical emergency was initially thought to be the problem, after a spectator at Central Coast Stadium suffered a suspected heart attack in the lead up to the match.
An ambulance had to be called, with paramedics arriving and taking the woman to Gosford Hospital.
But AAP has been told there are questions over whether paramedics had been properly booked for the event, meaning kick-off would have been delayed regardless.
Home clubs are responsible for booking paramedics for matches, with NRL guidelines requiring an intensive care unit paramedic and one other.
The NRL attempted to make calls to NSW Ambulance requesting personnel for the game, but they were unable to guarantee one at late notice.
After a 30-minute delay, a plea was eventually broadcast over the stadium's loudspeaker - asking for any intensive care paramedics in the crowd to come forward.
An intensive care paramedic and intensive care unit doctor presented themselves, with the NRL then weighing up whether the duo could be used to cover the match.
Eventually the game was given the go ahead, following a series of calls involving NRL hierarchy, senior medical staff and head of football Graham Annesley.
The NRL, who were making inquiries around the circumstances on Saturday evening, did not comment.
South Sydney CEO Blake Solly confirmed to AAP the club were looking into the matter.
"We're reviewing the circumstances of the delay to the start of the game, and we will comment when the review is complete," Solly said.
The episode comes after a similar issue occurred in the NRLW last year at a Parramatta home game.
When Saturday's game did start, Manly were the better undermanned team.
Hopoate was influential in the lead up to both their opening tries to winger Willett, putting him over for the first and making a break on the play before his second.
Fellow winger Raymond Tuaimalo Vaega also forced his way over for two tries, with the first the result of a nice ball from halfback Jake Arthur.
Clayton Faulalo scored another, while hooker Jake Simpkin pressed his claims for the No.9 jersey in round one against North Queensland when he crossed from a 20-metre dummy-half run.
Dodd did return to the field late for Souths, putting Declan Casey into space for a Bayleigh Bentley-Hape try and the Rabbitohs put on a flurry of points at the death.
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