The polytropic equation is derived using the ideal gas EOS, so it would probably not accurately describe a real gas in a thermodynamic process.
One way to analyze a non-polytropic process is by solving the energy balance between two states to get the temperature change of the working fluid, then using that temperature change in the equation of state to calculate the volume or pressure change. Solving the energy balance can get tedious if there are things like heat transfer and friction work though. For example, the heat transfer in a piston-cylinder expansion depends on the exposed surface area of the cylinder, which is constantly changing throughout the process. In my field, many of the terms in the energy balance are ODEs, so I end up doing a lot of numerical integration before actually solving the energy balance.
I was hoping others would chime in on this issue besides the two of us, but it doesn't look like there's a lot of interest in polytropic processes...