Southampton, who have won eight of their 10 games so far and top Group Two by seven points, raced into a 4-0 lead by the 54th minute with goals from Omar Rowe (2), Ryan Seager and Charlie Higgins.
However, Laste Dombaxe made it 4-1 a minute after Southampton's fourth goal and within 15 minutes it was 4-3 with Roman Michael-Percil and Victor Zapata-Caicedo on target.
Unfortunately, the fourth proved elusive.
Academy Manager, John McDermott, reported: "First of all, it was a chance for the lads who weren't involved in the NextGen game against Barcelona and there was a debut for goalkeeper Liam Priestley.
"We dominated possession but defended poorly on Southampton counter-attacks and set-plays ad they were extremely clinical.
"We had to make changes, Victor and Ruben Lameires had a positive impact off the bench and we got ourselves back to 4-3.
"Laste Dombaxe, who provided excellent leadership throughout, scored from the penalty spot after Roman Michael-Percil drove inside and was brought down.
"Roman made it 4-2, a tap-in after good work down the left from Victor and then Victor made it 4-3, this time from a Roman cross.
"We showed lots of heart and we had chances after that but the only disappointment was that although we had the momentum at that stage, we got a little impatient, when it was our patience and quality play that enabled us to get back into the game.
"The game went a bit ugly in the last 10 minutes, just through the lads trying too hard. If anything, we needed more of the same that got us back to 4-3.
"I was really pleased with Sam Smith, who had a positive game at left-back, Connor Ogilvie did well again and Filip Lesniak continued where he left off against Barcelona, where he was a substitute."
Spurs U18s: Priestley, Ward, Gardiner, Ogilvie, Smith, Lesniak, Dombaxe, Winks (Lameiras, 46), Michael-Percil (Sonupe, 76), Miller, Akindayini (Zapata-Caicedo, 25). Unused sub: McGee.