Division of Empire among-st his brother and thus weekning the position of king.
Humayun’s inability to understand the nature of the Afghan power and Sher Shah’s deceptive trick.
The presence of large numbers of Afghan tribes across the north India and their nature of getting united under a capable leader (like Sher Shah).
Without getting the support of the local rulers and zamindars, the Mughals were bound to remain numerically inferior.
The differences of Humayun with his brothers, and his alleged faults of character.
Though Humayun was a competent general and politician, his two mistakes i.e. ill-conceived Bengal campaign and wrong interpretation of Sher Shah’s proposal made him lose.