Background: By targeting immune cells rather than tumour cells, immuno-oncology therapies (IOs) have shifted the cancer treatment landscape offering the potential for long-term quality survival to many patients for whom treatment options were previously limited. Since the approval of immune checkpoint modulators in metastatic melanoma in 2011, a great deal of knowledge was generated on specificities of IO and many thereof remain challenging from market access perspective. Discussion: Pricing and reimbursement of IO therapies remain a key challenge for decision-makers due to immature evidence at time of market launch. IO therapies showed a delayed tumor response and potential long-term survival in some patients limiting use of standard endpoints (e.g. median overall survival, surrogate endpoints, such as progression-free survival) and raising much uncertainty on long-term efficacy data. Assessment of relative efficacy of IO therapies poses substantial challenges while fast evolving treatment patterns make evidence on successive lines becoming rapidly obsolete. IO response was reported as heterogeneous between patients; lacking predictive biomarkers precludes from selecting proper target populations. Immune-related side effects make long-term safety uncertain. IO response kinetic and heterogeneous populations in terms of survival are problematic vis-à-vis standard methods used to extrapolate survival data. Anticipation of potential budget impact is more complex by uncertainty in dose selection, unclear rules for treatment hold/discontinuation and increasing number of potential drug combinations. Finally, given IO potential for long-term quality survival, decision-makers should consider a societal perspective to fully capture indirect costs, such as work productivity and caregiver time. Conclusions: Recognition of entire benefits of IO therapies depends largely upon addressing the discussed challenges. Mature and long-term clinical data are needed to quantify additional benefits and to support decision-making. On-going research and debates on new clinical endpoints, specific survival extrapolation methods, research on biomarkers, drug value frameworks should contribute to addressing gaps in IO assessment.