**Abstract**

Colorectal cancer (CRC) remains one of the most frequently diagnosed tumours worldwide. Despite advances in surgical intervention and therapeutics, development of chemoresistance remains a challenge to treating CRC. Predicting treatment response in CRC has strongly relied on genomics, transcriptomics and epigenomics, combined with different cancer staging and classification systems. Despite being beneficial, these omics technologies fail to provide any assessment at a protein level. Thus, having high-throughput tools that assess tumour response to therapy at a protein level will definitely complement the current approaches. In this regard, the field of proteomics holds promise to understand treatment response in tumours. Additionally, patient-derived tumour organoids are replacing the traditional cell lines and xenograft models as the preferred *in vitro* models for predicting clinical response due to being a better representative model of typical tumour characteristics *in vivo*. Combining proteomics and tumour organoids can provide more personalised and optimal treatments for CRC in the coming years. This chapter aims to provide an overview of the progress made in proteomic research and use of organoids for understanding CRC treatment response, together with discussing the strengths and limitations of these two approaches when linked together. This overview will then be used to propose future perspectives.

**Keywords:** colorectal cancer, proteomics, organoids, treatment response, prediction
