Improvement of energy conversion efficiency in prime movers has become of fundamental importance in order to respect EU 2020 targets. In this context, hybrid power plants comprising combined heat and power (CHP) prime movers integrated with the organic Rankine cycle (ORC) create interesting opportunities to additionally increase the first law efficiency and flexibility of the system. The possibility of adding supplementary electric energy production to a CHP system, by converting the prime movers’ exhaust heat with an ORC, was investigated. The inclusion of the ORC allowed operating the prime movers at full-load (thus at their maximum efficiency), regardless of the heat demand, without dissipating not required high enthalpy-heat. Indeed, discharged heat was recovered by the ORC to produce additional electric power at high efficiency. The CHP plant in its original arrangement (comprising three internal combustion engines of 8.5 MW size each) was compared to a new one, involving an ORC, assuming three different layout configurations and thus different ORC off-design working conditions at user thermal part-load operation. Results showed that the performance of the ORC, on the year basis, strongly depended on its part-load behavior and on its regulation limits. Indeed, the layout that allowed to produce the maximum amount of ORC electric energy per year (about 10 GWh/year) was the one that could operate for the greatest number of hours during the year, which was different from the one that exhibited the highest ORC design power. However, energetic analysis demonstrated that all the proposed solutions granted to reduce the global primary energy consumption of about 18%, and they all proved to be a good investment since they allowed to return on the investment in barely 5 years, by selling the electric energy at a minimum price equal to 70 EUR/MWh.