If I understand your question correctly, I think the answer is yes. If the SME box is functioning as a forwarding router, and your real web server is on another machine, then port assignment and IP addresses determines which ports direct traffic to which machines.
I have similar set up in which I have two machines each with a different type of web server: one with SME; another with Abyss Web Server.
In my case, I have a separate router (a Linksys) which forwards inbound traffic to the appropriate PC/web server. To really make this even easier, I use ZoneEdit.com to direct inbound URLs to the port I want to feed into the router so it can forward to the correct PC/web server.
'Hope this helps you.