This Special Issue aims at interrogating the judicial and extra-judicial challenges that arise from the EU complex administrative framework, which can be characterized as both multi-level—arising from the vertical cooperation between EU and national authorities—and cross-level—arising from horizontal cooperation between national authorities themselves. It starts from the premise that there may be decisions affecting natural and legal persons which cannot be easily reviewed judicially, whereas in extra-judicial cooperation, the lack of common standards or practices across Member States may undermine the effectiveness of EU policies and objectives. This Special Issue focuses on various mechanisms of horizontal and vertical cooperation, such as regulatory patterns giving rise to transnational administrative acts and mutual recognition systems, case studies of composite procedures in the field of the genetically modified organisms regime and information sharing in asylum policy, as well as multi-level inspection activities for the enforcement of EU law. It further complements the analysis on the judicial challenges arising from those cooperative structures with an examination of extra-judicial avenues of control in the EU administrative framework, namely the “EU queries” process and the cooperation of ombud offices, as well as the audit of the EU budget. This Special Issue reflects on ways to overcome the current challenges of, and seeks to prompt further research on, the multi-layered EU system of administrative cooperation.