Spurs invited early pressure on themselves, looking far different from the organised unit we're so used to seeing in the league with possession frequently changing hands in the initial stages.
Mauricio Pochettino was forced into an early substitution with Vincent Janssen coming on for Moussa Demeble only 30 minutes in, which saw Son drop from his makeshift role up-top.
Kyle Walker gifted the best chance of the half to Leverkusen with a poor clearance playing in Brandt only for Vertonghen to make two crucial blocks first that of Brandt's shot and then the rebound hit from Hernandez.
Just short of the stroke of half-time Alli saw his goal disallowed after being played by Janssen who had fouled his man in the set-up.
Tottenham kicked off their second-half in far better fashion than the first with Alli appealing for a foul just inside the box, which the referee waved away as Eriksen's follow-up shot from distance looked like it was creeping in, but fell just wide of the post.
The London side then had a minor call for a penalty after some shirt tugging between Tah and Janssen. Before a surging run from Walker saw everything fall right apart from the
Eric Dier then caused some trouble for his side only for Hugo Llrois to save Spurs again, much like in the reverse fixture in Germany.
However, the French shot stopper couldn't stop Kampl's effort after
Eric Dier, who had been below par for the majority of the game, looked to have brought his side back in the game after he struck a great free-kick only to strike the bar, similar to the goal he scored for England over the summer.
Dutch striker Janssen then looked set to capitalise on the rebound, but failed to do score as Bayer 04's defence scrambled the ball away to maintain their lead.
Tottenham Lineup: Lloris, Walker, Dier, Vertonghen, Davies, Wanyama, Dembele (Janssen 30'), Sissoko, Alli, Eriksen (Winks 66'), Son (Nkoudou)
Bayer Leverkusen Lineup: Leno, Henrichs, Toprak, Tah, Borges, Kampl, (Volland 85') Baumgartlinger, Aranguiz (Havertz 86'), Brandt, (Calhonoglu 70'), Mehmedi, Hernandez