The Arduino Nano uses a bootloader for handling programming the MCU, which requires the USB to serial bridge to be disconnected from anything that could interfere with the programming.

That's because the Arduino Nano 3.0 is intended for breadboarding, where the compact dimensions will leave more space for other components.

The board is built around an ATtiny3217 and has almost all of the Nano’s features, like a USB port, reset button, built-in LEDs, 5 V regulator, and preloaded bootloader.