Following a century of major discoveries on the mechanisms determining meat colour and tenderness using traditional scientific methods, further research into complex and interactive factors contributing to variations in meat quality is increasingly being based on data-driven “omics” approaches such as proteomics. Using two recent meta-analyses of proteomics studies on beef colour and tenderness, this review examines how knowledge of the mechanisms and factors underlying variations in these meat qualities can be both confirmed and extended by data-driven approaches. While proteomics seems to overlook some sources of variations in beef toughness, it highlights the role of post-mortem energy metabolism in setting the conditions for development of meat colour and tenderness, and also points to the complex interplay of energy metabolism, calcium regulation and mitochondrial metabolism. In using proteomics as a future tool for explaining variations in meat quality, the need for confirmation by further hypothesis-driven experimental studies of post-hoc explanations of why certain proteins are biomarkers of beef quality in data-driven studies is emphasised. •Insights from both conventional studies and proteomics into beef meat colour and tenderness are reviewed•Proteomics meta-analysis of variations in beef colour highlights energy metabolism pathways•Energy metabolism and proteolysis emphasised in proteomics of beef tenderness•Calcium regulation, oxidation and nitrosylation pathways also prominent in tenderness•Increasing evidence points to a strong role of post-mortem mitochondrial metabolism in meat quality•Potential mechanisms suggested by data-driven experiments must be checked by hypothesis-driven studies