See the question and my original answer on StackOverflow

From the IISNode wiki here what is iisnode

iisnode is a native IIS module that allows hosting of node.js applications in IIS on Windows.

Behind the scene, IISnode is how Microsoft host node.js applications on its cloud platform Azure. More on this here: Node.js on Windows Azure & iisnode

Note Azure is not mandatory, you can host node.js on plain IIS without Azure, but Microsoft had to develop this to be able to host node.js in a very scalable way. The wiki page lists all advantages of IISnode.

That has nothing to do with ASP.NET. ASP.NET can also be hosted on IIS, but it's a complete different architecture. You can mix both on the same machine, but they are not closely related.