In its landmark judgment in the case of Achmea (judgment of 6 March 2018, case C-284/16 [GC]), the Court of Justice adjudicated that Investor-State Dispute Settlement (ISDS) adversely affects the autonomy of EU law. Accordingly, ISDS clauses in international investment agreements that contravene Arts 267 and 344 TFEU and the principles of mutual trust and sincere cooperation enshrined in Arts. 19, para. 1, and 4, para. 3, TEU are inapplicable under EU law. However, the reasoning of the Court of Justice in Achmea did not convince international investment tribunals that they lack jurisdiction in intra-EU investment disputes. This opposition calls for clarification of the different principles underpinning the EU legal order and international investment law. This Article presents a debate between these two legal orders, which unfolds around three separate, albeit related issues: the status and applicability of the EU and the Member States’ international agreements within the EU legal order; the manner in which the Achmea judgment must be interpreted and its application in the international investment law context; and the meaning and relevance of the concept of the autonomy of EU law as the key issue in defining the relationship between EU law and international investment law.