The popularity of Remotely Piloted Aircraft Systems (RPAS) is growing at an increasing rate as an alternative to manned aviation for different purposes and applications. So far, most of their operations have been of military character, but the demand for civil and commercial applications is growing exponentially. RPAS have been allowed to operate in segregated airspace by restricting other users from entering the volume associated to the operation of the RPAS. This temporary solution based on accommodating their operations on a case-by-case basis is not feasible on the long-term. Moreover, the latest forecast carried out by SESAR Joint Undertaking (SJU) reveals that by 2050 RPAS will represent 20% of the fleet. The available airspace is a scarce resource and is already saturated, which means that additional unmanned operations would not be possible simultaneously. Integration in non-segregated airspace is the only manner in which the full benefits and capabilities of RPAS will be achieved, while maintaining the same levels of safety and efficiency as manned aviation. In order to achieve a safe, efficient and transparent integration, a common regulatory framework and new technologies are currently under investigation. However, neither operational nor performance standards of RPAS integration have been addressed properly. For that reason, this project is focused on the development of a methodology to determine minimum operational and performance requirements by assessing the impact of RPAS operations on the Air Traffic Management (ATM) Network. The scope is limited to the en-route phase as a starting point since none of the flight phases have been analysed yet. This project is carried out in collaboration with EUROCONTROL. RPAS are well known for presenting a wide range of performance characteristics, especially in terms of cruise speed and rate of climb. Thus, two different unmanned performance models have been chosen from the available performance models in the EUROCONTROL database: RP01 (MQ-9), which presents a similar performance to commercial aviation aircraft, and RP02 (RQ4A), which is considered a low-performance RPAS in terms of cruise speed and rate of climb. Building on a base scenario in the Paris Control Terminal Area (CTA),Monte Carlo simulations of the air traffic have been performed in order to randomly vary the main input variable: the set of en-route flights that is substituted by unmanned aircraft. Two different scenarios have been analysed separately in order to establish the requirements: one for same-performance RPAS, and the other for low-performance RPAS. In order to assess the impact, three different Key Performance Areas (KPAs) have been selected: capacity, efficiency and safety. These KPAs are in turn characterized by their corresponding Key Performance Indicators (KPIs), namely sector capacity, sector overload, flight time efficiency, flight path efficiency and number of potential conflicts. Based on an analysis of the current occupancy of the flight levels, operational requirements are defined in terms of altitude segregation. RPAS are not allowed to operate in the most occupied flight levels (FL): from FL300 to FL400. Therefore, depending on their operation and performance characteristics (i.e. ceiling), they will adapt their cruise FL to operate below FL300 or above FL400. The optimal value of performance requirements for same-performance RPAS has been found to be a minimum cruise speed of 390 kts, while for low-performance RPAS this minimum cruise speed is of 280 kts. Additionally, for low-performance RPAS, it is found that the rate of climb of 1,000 fpm results in the best performing case when changes in FL are required. The results show that the values of the key performance indicators for the base scenario are difficult to reach when RPAS are sharing the airspace. However, the establishment of minimum operational and performance requirements contributes to a significant reduction of the negative impact that the integration of RPAS operations implies. The development of this methodology and its application to the characteristics of each airspace sector will contribute to the full integration of RPAS in non-segregated airspace.