Key changes in the pharmacoepidemiological research environment had a significant influence on the activities of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) over the last decade. These changes included the SARS-CoV-2 pandemic, the increased access to data sources, the integration of real-world evidence (RWE) into regulatory and public health decision-making, and the emergence of new technologies and methods. This paper describes how ENCePP has evolved in this changing environment to strengthen pharmacoepidemiological methods and practice in Europe and globally. It also provides future perspectives for the network. Through a collaborative approach in non-interventional research, ENCePP will collectively continue to promote excellence for RWE generation, supporting the safe and effective use of medicines.