Treatment of complex diseases has largely emerged from historical, empirical medical science which involved simplistic models of disease generated in animal models, which aimed to reflect some elements of the human disease in a rather mechanistic sense. For example in autoimmunity, Rheumatoid Arthritis and Multiple Sclerosis, the mouse models of CIA and EAE are very artificial and in many ways do not truly reflect the human disease either in terms of aetioogy, length and duration and evolution of the disease or even all the characteristics (biomarkers) of the disease. In addition these models sometimes do not even reflect disease responsiveness in the same way to certain therapies and may give contradictory results. In immuno-oncology we are also faced with models that do not reflect the same micro-environment as we would have in human cancer. Response to immunotherapy cannot always be predicted on the basis of such models which historically have predicted tumor response with many targets that have failed to materialize in the human setting. Humanizing the drug discovery process with more relevant model in human tissues can provide sometimes better insight into disease outcomes. Furthermore reductionist approaches can be misleading and more holistic multidimensional models with multimodal therapies are needed to improve outcomes in complex diseases like autoimmunity and Immunol-oncology. The inter play of multiple cellular mechanisms and cytokines needs to be better understood to devise breakthrough therapies. Sometimes this is possible with the identification of a single molecular target that has multiple actions or in other cases identification of two or more targets that have potential for synergy. Current targets both in autoimmunity and in immune-oncology have largely focused on single molecular targets and biological redundancy has not been taken into account leading to multiple failures in autoimmunity and immune-oncology. Multiple examples of how this has gone wrong across academia, biotech and big pharma are available with many recent failures and billions of dollars of value evaporated from medical research. A more cost effective model will be demonstrated on using high quality clinical science using multiple dimensions to produce breakthrough therapies.