Recent advances in immuno-oncology research have revolutionised our understanding of the interplay between immune cells and the tumour microenvironment (TME), profoundly impacting patient responses to therapy. The TME, comprising tumour cells, immune cells, extracellular matrix, stromal cells, and co-existing microbes, orchestrates the immune phenotype of cancers, shaping disease progression and treatment outcomes. Immune-cell infiltration serves as a significant prognostic marker in various cancers, with higher rates correlating with improved prognosis. Recent discoveries have paved the way for immune checkpoint blockade therapies, which exhibit remarkable efficacy across multiple cancer types. However, understanding the nuanced contributions of different immune-cell populations to therapeutic responses remains a challenge. The majority of research has focussed on the role of T cells in the immune response to cancer therapies, with the potential importance of B cells only recently being recognised. Here, we review the diverse phenotypes of B cells within the TME, their structural organisation within tertiary lymphoid structures (TLS), and the role of both B cells and TLS in cancer prognosis and response to different therapies for cancer treatment.