Bladder cancer has an increasing incidence in North America and represents a significant healthcare burden. At the molecular level, it is a diverse disease with heterogeneous clinical outcomes and treatment responses. Immunohistochemistry (IHC) has been applied to predict molecular subtypes with good reliability. In our previous study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, to predict molecular-based luminal versus basal subtypes of bladder cancer. Our previous proteomics studies have also identified a list of potential proteins associated with the patients’ prognosis and chemotherapy response. The overall objective of the current study is to identify an IHC marker panel to accurately predict the molecular subtypes of bladder cancer and their response to chemotherapy. This proposed study will demonstrate that IHC markers could reliably identify the luminal and basal molecular subtypes. The semi-quantitative visual assessment of these markers in routine pathological preparations will be a valuable tool in identifying bladder cancer’s molecular subtypes and improving the selection of MIBC patients most likely to benefit from neoadjuvant chemotherapy.