The applications of zeotropic mixtures and multi-evaporator systems are two viable options to improve the performance of the organic Rankine cycle (ORC). This paper conducts the thermo-economic comparison of a basic ORC with R245fa/R600a and a parallel double-evaporator organic Rankine cycle (PDORC) with R245fa. Four indicators are used to evaluate the system performance: net power, cycle efficiency, area of heat exchangers, and area of heat exchangers per net power output. Submodels of condensers and evaporators are established specially for pure organic fluids and zeotropic mixtures. The performance optimization using genetic algorithm is conducted to compare the two systems quantitatively. The optimization indicates a zeotropic mixture is more profitable than a pure work fluid in a basic ORC with a worthy additional investment of heat exchanger. Though PDORC can increase net power obviously, it would decrease the thermo-economic performance of ORC.