Urothelial bladder carcinoma is a cancer type featuring a pronounced heterogeneity. Two major types, the Non-Muscle-Invasive Bladder Carcinoma (NMIBC) and the Muscle-Invasive Bladder Carcinoma (MIBC), differ in both their respective mutational spectra and probable cells of origin, as well as clinical courses and therapeutic strategies. Genome-wide transcriptomic characterization and the resulting molecular subtypes revealed essential differences in the underlying biology, with a profound impact on clinical behaviour. The increasing awareness of cellular complexity of especially MIBC lead to new insights into tumour-stroma interactions, with carcinoma-associated fibroblasts likely playing a prominent role in most tumours. There are numerous intertwined signalling cooperation mechanisms between carcinoma and stroma cells that have been characterized hitherto. The basic research is accompanied by a remarkable clinical development resulting in gradually increasing availability of new therapeutic strategies, be it bladder-sparing trimodal therapy, the use of specific signalling inhibitors, antibody-drug conjugates or immune checkpoint inhibitors that unleash existing anti-tumour immune response. Strikingly, the dramatic differences in responses seen in individual patients treated with these novel therapeutic modalities underscore the concept of urothelial bladder carcinoma heterogeneity, in part reflecting the known biological heterogeneity such as molecular subtypes or stromal involvement. Further parallel clinical and basic research is thus highly warranted to understand and forecast possible clinical behaviour of each tumour and to increasingly individualize care for urothelial carcinoma patients.