The drug development process in oncology has significantly evolved in the last decade with the clinical investigation and approval of immuno-oncology therapies, providing new treatment modalities in various cancer types to patients. These efficient and promising treatments have in parallel benefited from the new regulatory accelerated approval paths, giving patients access to these cancer drugs in a relatively short period of time. While progress is made to understand and manage the side effects of these therapies, the unique safety profile and variable time to onset of the adverse effects lead to a re-think of how dose escalation designs could be adapted for these new molecular entities. Model-based designs seem to be particularly suitable to include specific features that could help assess the safety and tolerability of immuno-oncology agents. These models aim to provide a better estimate of tolerable doses for long-term treatment with immuno-oncology therapy and some, such as the mDA-CRM and the TITE-CRM, have the potential to even reduce the time taken by the clinical investigation process.