If there are 2 NICs on the same machine, can a TCP client on one NIC connect to a TCP server on the other NIC?

I use TUN/TAP to create a tun NIC tun0 with IP 10.10.10.2, and I have a real NIC eth0 with IP 202.112.34.49

Then I run a TCP client which binds its socket to 202.112.34.49 and a TCP server binding 10.10.10.2. but I can't establish a tcp connection between them.

So can a TCP client on one NIC connect to a tcp server on the other NIC?

Packets to local addresses will always run on the lo interface; they will never leave the machine. (Packets to local addresses arriving on non-lo interfaces are regarded as martians.)

In other words, your packets must get stuck on the lo interface somewhere, possibly due to a firewall. Check your iptables-save output and do a tcpdump on the lo interface for those packets to debug this issue.

Neither the TCP client nor the TCP server are "on" any NICs. Individual interfaces are considered at layers 1 and 2 while TCP operates at layer 4. Except for very special socket options like SO_BINDTODEVICE, TCP endpoints are not attached to any network interface.

Your TCP server and client just happen to be bound to different local IP addresses. Connecting between them should work just fine.