Usually, when we deal with topics like this within the Marvel universe, it is usually through interesting theories. But they end up being theories, after all. However, today we can say that it is more than that.
Basically, thanks to the information that comes from the Marvel comics themselves. And in these, a lack of Red Skull is detailed according to which it is impossible for the villain to get hold of the Soul Stone in Avengers: Infinity War. Can you imagine what it could be about?
But let's go by parts. As you well know, the Soul Gem is, without a doubt, one of the most difficult to obtain. This occurs because it is necessary to sacrifice someone you love to get it. UCM lovers discovered its existence in Infinity War, where Thanos moved to Vomir in order to get it (paying the price Gamora, his own daughter). However, there was also Red Skull (played by Ross Marquand), who was the guardian of such precious power.
But … why couldn't he get the Gem and Thanos could? Basically because Gamora was wrong when she thought that her father was not capable of loving anyone. Something that, according to Marvel comics (via ScreenRant), Red Skull is not capable of. And for that reason, the villain had no one to sacrifice to. It is sad and very logical, but it is so.
Where exactly is that information revealed? Specifically, in the Captain America comic number 298. In that number, the villain thinks he has fallen in love with a woman. Worse, when rejected, he even attacks her. Years later, he admits that he never felt love, but lust. And he decides that, since then, he will never love again; not even her own daughter Sin.
In fact, at all times (and also in the movies), it stands out that the only thing that matters to Red Skull is just the opposite of love. Specifically, his hatred for Steve Rogers. And that could be, precisely, the reason why the Space Gem chose him as guardian for the Soul Gem. The less interesting, huh?