Sundowns were drawn in Group A alongside former coach Pitso Mosimane's Al Ahly and two Sudanese clubs in Al-Hilal and Al-Merrikh.
The competition's group stages are set to get underway in February 2022.
"The group we find ourselves in is a really interesting group with probably three previous winners of the Champions League before and African champions," Mngqithi said.
"Al-Hilal we played against them in the group stages last season. We also have Al-Merrikh again, and the challenge in our group is it involves extensively travelling to Sudan.
"That is where our biggest challenge might be, but you cannot take any team lightly because if you look at the other groups you will realise that they are all very difficult with stiff competition.
"But otherwise, it's a group we will fight very hard to get through, we are confident as a technical team and players that the group that we have is capable of advancing.
"We will work very hard towards that because it's not going to be easy.
"Al Ahly gave us trouble last year and knocked us out of the quarter-finals last year, and that on its own is suggestive of the challenges we are going to face."
Mamelodi Sundowns are set to return to first-team training during the second week of January after being given an extended break over the festive season.