Human beings often face the reality of their own limitations when confronting the infinite nature of God. There is a profound sense of smallness that comes from realizing the sheer scale of divine awareness, an awareness so vast and total that it remains entirely beyond human reach.
The primary approach among commentators is to view this reality as the massive gap between God's knowledge and human understanding. God possesses an awareness that completely surrounds a person from every possible direction. He examines humanity so deeply that absolutely no part of a person remains hidden or unexposed. For a human being, trying to grasp this level of total divine knowledge is simply impossible [ביאור שטיינזלץ]. This inability to understand exists on two distinct levels. The first is a basic sense of wonder regarding things that might theoretically be understood but remain hidden from a specific individual. The second, deeper level is an absolute, supreme mystery that is fundamentally beyond the capacity of any human mind, no matter how great [מלבי״ם].
Some focus this supreme mystery on the physical creation of the human body itself. The human form is composed of completely opposing natural forces: heat and cold, moisture and dryness. The divine wisdom required to perfectly blend these contradictory elements together in order to sustain life is an exalted concept that no person can truly comprehend [רד״ק].
A different perspective connects this profound limitation to the realization that one can never escape God. The knowledge that remains completely hidden from humanity is the knowledge of how to run away or where to find shelter from His presence [רש״י]. Because God encompasses a person on every side, any strategy or attempt to find a hiding place is doomed to fail. This is especially true when a person commits a wrong and desperately seeks to hide. The task of escaping God's view is simply too difficult, and finding a way to do so is something a person will never be able to figure out or achieve [מצודת דוד, מאירי].
A completely different and unique approach takes these concepts out of their direct context and reads them as an allegory for the sin of the Tree of Knowledge. In this view, the speaker is the first man, Adam, and he is talking about Eve. The wondrous, hidden knowledge refers to the extra measure of understanding that was given to the woman when she was created, an understanding that surpassed his own. Adam is confessing that Eve overpowered him and was too strong for him to resist. When she tempted him to eat the forbidden fruit, he simply could not stand against her, effectively placing the primary blame for the first sin squarely on her shoulders [אלשיך].