Despite the fact that chronic diseases usually occur together with a spectrum of possible comorbidities that may differ strongly between patients, they are classically still viewed as distinct disease entities and, consequently, are often treated with uniform therapies. Unfortunately, such an approach does not take into account that different combinations of symptoms and comorbidities may result from different pathological (e.g., environmental, genetic, dietary, etc.) factors, which require specific and individualised therapeutic strategies. In this opinion paper, we aim to put forward a more differentiated, systems medicine approach to disease and patient treatment. To elaborate on this concept, we focus on the interplay of tinnitus, depression, and chronic pain. In our view, these conditions can be characterised by a variety of phenotypes composed of variable sets of symptoms and biomarkers, rather than distinct disease entities. The knowledge of the interplay of such symptoms and biomarkers will provide the key to a deeper, mechanistic understanding of disease pathologies. This paves the way for prediction and prevention of disease pathways, including more personalised and effective treatment strategies.