What does John 12:39 mean?

When God judged the nation of Egypt, He did so by hardening the heart of the Pharaoh (Exodus 9:12). This caused the Egyptian ruler to be even more resistant to God, and that resulted in further plagues. Key to this fact is noting that Pharaoh had already been cruel and resistant and had in fact hardened His own heart first (Exodus 7:13, 7:22; 8:15; 8:19; 8:32). It is not until after the sixth plague that God is said to have actually "hardened the heart" of Pharaoh. This means that one way in which God judges willing disbelief is by perpetuating it (Proverbs 29:1). Those who stubbornly rebel against God may find themselves in a state where they cannot believe, as judgment for their earlier refusal to believe.

John's gospel has mentioned the famous "Suffering Servant" of Isaiah chapter 53. In that prophecy (Isaiah 53:1), Isaiah asks "who has believed what he heard from us?" The expected answer is, "no one," in the sense that the Messiah is broadly rejected by His own people and the world at large (Matthew 23:37; Romans 10:16–21).

All of this plays into the use of the word "therefore" as found in this verse. The only reason—the explicitly stated cause—for those who "could not believe" is their prior commitment to unbelief. They cannot now believe because they would not believe when given the chance. What John cites from Isaiah 6:10, in the following verse, is in that very context.