Spurs will visit Signal Induna, but without the influential Kenyan Captain who also missed out on the first leg at Wembley Stadium.
Wanyama is yet to shake off a nagging knee injury he sustained early in August.
The former Southampton and Celtic midfielder has featured only twice for Spurs this season in all competitions; his last appearance for Mauricio Pochettino coming in a 2-1 defeat to champions, Chelsea in the domestic competition.
Pochettino will also have to do without Toby Alderweireld who is also nursing a hamstring injury, though Danny Rose is available for selection.
Spurs have already booked a place into the next stage, but a win over the Germans will see them top the group and land a relatively 'weaker' opponent.