A USB flash drive is just storage for private keys. It means that when you want to make a transaction, you must attach your drive to the computer and let your bitcoin software read the keys from the device. At this point, your private keys are accessible to viruses and malware, just as to any other software on your desktop computer.
On the contrary, TREZOR is a single-purpose computer, which stores your private keys and actively signs transactions without sending your private keys to the computer. When you want to make a bitcoin transaction, your bitcoin software just sends a transaction template to the TREZOR device and asks for a digital signature. TREZOR shows the requested amount and target address on its display. You will then confirm the transaction by pressing the hardware button. TREZOR will sign transaction internally and send the digital signature back to the computer, without leaking your private keys.
Thanks to this, you can use TREZOR even on a vulnerable or hacked computer.
Source: Official website of Trezor – https://trezor.io