The departure of the UK from the European Union (EU) and affiliated European regulatory bodies on the 31st December 2020, including the European Medicines Agency, (EMA), has resulted in the Medicines and Healthcare products Regulatory Agency (MHRA) becoming an independent national regulator. This has required a fundamental transformation of the UK drug regulatory landscape, creating both opportunities and challenges for future oncology drug development. New UK pharmaceutical policy has sought to establish the UK as an attractive market for drug development and regulatory review, by offering expedited review pathways coupled to strong collaborative relations with other leading international medicines regulators, outside of Europe. Oncology is a key global therapy area for both drug development and regulatory approval, and the UK government has been keen to demonstrate regulatory innovation and international collaboration in the approval of new cancer medicines. In this review, we examine the new UK regulatory frameworks, policies, and global collaborations affecting new oncology drug approvals following departure from the EU. We explore some of the challenges which may lie ahead as the UK forges ahead with new and independent regulatory review and approval processes for the next generation of cancer medicines.