To be profitable, a geothermal energy system must effectively and economically convert a given resource into useful energy services to be delivered to the consumer during different periods of the year. These services include electricity, district heating, and cooling. The performance of the system depends not only on the specific climate conditions and resource characteristics, but also on multiple interdependent decision variables that affect the thermodynamic and economic performance of the system. These decision variables include the conversion technologies and their associated operating conditions, as well as the different resources that are potentially exploitable at a given location. Therefore, the optimal exploitation schemes of geothermal resources are best identified using thermo-economic modeling which integrates models for the resources, the conversion technologies, and multiple demand profiles. This paper proposes a strategy to identify optimal exploitation schemes of geothermal resources using a multi-period approach, integrating the superstructure of exploitable resources with the superstructure of conversion technologies and multiple demand profiles. A general case study is considered for the validation of the approach. The superstructure of resources consists of an enhanced geothermal system, a deep aquifer, and a shallow aquifer. Organic Rankine cycles and both single and double flash steam cycles, which can be used for combined heat and power production, are considered within the conversion technology superstructure. Heat pumps are also considered. A back-up boiler is also included in case the geothermal resources alone cannot fully satisfy the demand. Periods identified for the demand profiles of district heating and cooling are summer, winter, inter- seasonal, and extreme winter and summer conditions. Considering thermodynamic and economic objectives, process integration techniques in conjunction with an evolutionary algorithm are employed to determine the optimal exploitation schemes and system configuration across the multiple periods. The proposed strategy can be adjusted for specific locations and conditions, and could potentially serve as a tool for evaluating the exploitation potential of a variety of geothermal resources and aid in future decision-making processes.