The pair both started against Manchester United but neither were on the pitch for the late drama as Matthijs de Ligt scored in the sixth minute of stoppage time to make it 2-2 in north London.
That came after Richarlison had put Spurs in front in the 91st minute, whipping his shirt off as Spurs wildly celebrated what had looked set to be a dramatic victory.
Romero was replaced by Kevin Danso with a couple of minutes of normal time remaining. He was an animated figure on the touchline, conducting the defenders from the technical area and then charging onto the pitch in celebration for Richarlison's goal.
"Yeah, he was just done physically," Frank said of the decision to bring off Romero.
"He just came back from that injury. He's fine."
Frank also confirmed that Romero would fit to join up with Argentina for international duty.
On whether Spurs missed him at the back when conceding from a corner in the final seconds, Frank added: "Yeah, but I think his position, he wouldn't have been near the goal anyway.
"So it's a cross on the side and then he would have been in the middle zone, so this was back post, so that wouldn't have affected anything."
Kolo Muani, meanwhile, started up front with Richarlison on the left wing, but the Frenchman was replaced by Wilson Odobert at half-time.
Explaining that, Frank said: "He actually struggled a little bit, but nothing big."
Mohammed Kudus was not involved at all on Saturday but Frank is confident winger will be available for selection against Arsenal after the international break.
"The knock, just too short a turnaround," he said. "Keeping him out for Tuesday game and this game. Very confident that he should be available for the next one."