The great successes achieved by cancer immunotherapy cannot hide the fact that most patients do not respond to the treatment. A better understanding of the tumor microenvironment (TME) is a prerequisite for rational drug development and the discovery of more informative biomarkers. Previous efforts aimed at unraveling the human TME have either been limited by the choice of profiling modalities or by insufficient patient numbers. In addition, whereas much work focused on subjects with earlier disease stages, patients with unmet medical need often suffer from advanced cancer that is less well understood. Here, we introduce the IMMUcan project, a European Union-funded, public-private consortium. The aim of IMMUcan is to generate a tumor atlas focusing on patients with unmet medical need. IMMUcan will integrate molecular profiling data and cellular spatial data derived from multiplex immunofluorescence and imaging mass cytometry analyses. These data can contribute to a better understanding of treatment resistance mechanisms, help define patient populations that are likely to benefit from current therapeutic interventions and identify determinants of the tumor immune landscape composition. Finally, the characterization of altered biological pathways and molecular targets will inform precision oncology approaches and guide drug combination strategies for individual patients.