Is there a way to determine the difference between a BTC prefix 3 address and a LTC prefix 3 address? I am trying to determine if there is a way to tell the difference between a BTC prefix 3 address and a LTC prefix 3 address, for validation purpose.

Example if given this public key address:
3HpwVq6zSd3wxSrAypFYJGKE2JTm3fvuC9

Would there be a way to definitively say it is a BTC or LTC address?
No, there is not. There isn't anything network specific about an address. Such addresses can be used on both Bitcoin and Litecoin. You could also spend both the Bitcoin and Litecoin associated with that address so long as you have the private key. Because Bitcoin and Litecoin use the same Elliptic Curve and the same scripting system, all you would need to do is to export the private key from one wallet and import it into the other.