Within the ovarian follicle, mammalian oocytes acquire the necessary molecular machinery for successful fertilisation and embryonic development. In the absence of the follicle, oocytes matured in vitro (IVM) using traditional IVM show compromised developmental competence, resulting in poorer outcomes for patients. A novel in vitro system (CAPA-IVM) using c-type natriuretic peptide provides the oocyte with extended time to develop, with improved success rates. Here, we interrogate constituents of oocyte developmental competence by comparing the proteomic signature of mature mouse metaphase II (MII) cumulus-oocyte complexes (COCs) of differing intrinsic qualities, as matured by various maturation protocols. We employed label-free mass spectrometry to analyse the proteomes of mouse oocytes and cumulus cells separately. Proteomic profiling identified around 1600 proteins in oocytes and 3100 in cumulus cells across all three treatment groups (at least 2 peptides per protein). Differential expression analysis and pattern analysis collectively revealed a signature of proteins that were consistently differentially expressed between in vivo and in vitro oocyte maturation systems (log2FC of ± 1 and a p-value ≤ 0.05). These subsets of proteins were mapped to biological processes including eukaryotic translation, autophagy and endocytosis pathways within oocytes. Changes in reactive oxygen species detoxification and serine biosynthesis were observed in cumulus cells. Altogether, these findings provide new insights into the proteomic mechanisms underpinning oocyte developmental competence, with the potential to improve clinical oocyte diagnostics, expand on current clinical maturation systems and provide novel therapeutic options to infertile patients.