Bladder cancer is one of the most common cancers worldwide. Despite its high incidence, cystoscopy remains the currently used diagnostic gold standard, although it is invasive, expensive and has low sensitivity. As a result, the cancer diagnosis is mostly late, as it occurs following the presence of hematuria in urine, and population screening is not allowed. It would therefore be desirable to be able to act promptly in the early stage of the disease with the aid of biosensing. The use of devices/tools based on genetic assessments would be of great help in this field. However, the genetic differences between populations do not allow accurate analysis in the context of population screening. Current research is directed towards the discovery of universal biomarkers present in urine with the aim of providing an approach based on a non-invasive, easy-to-perform, rapid, and accurate test that can be widely used in clinical practice for the early diagnosis and follow-up of bladder cancer. An efficient biosensing device may have a disruptive impact in terms of patient health and disease management, contributing to a decrease in mortality rate, as well as easing the social and economic burden on the national healthcare system. Considering the advantage of accessing population screening for early diagnosis of cancer, the main challenges and future perspectives are critically discussed to address the research towards the selection of suitable biomarkers for the development of a very sensitive biosensor for bladder cancer.