Monitoring molecular dynamics of an organism upon stress is probably the best approach to decipher physiological mechanisms involved in the stress response. Quantitative analysis of proteins and metabolites is able to provide accurate information about molecular changes allowing the establishment of a range of more or less specific mechanisms, leading to the identification of major players in the considered pathways. Such tools have been successfully used to analyze the plant response to cadmium (Cd), a major pollutant capable of causing severe health issues as it accumulates in the food chain. We present a summary of proteomics and metabolomics works that contributed to a better understanding of the molecular aspects involved in the plant response to Cd. This work allowed us to provide a finer picture of general signaling, regulatory and metabolic pathways that appeared to be affected upon Cd stress. In particular, we conclude on the advantage of employing different approaches of global proteome- and metabolome-wide techniques, combined with more targeted analysis to answer molecular questions and unravel biological networks. Finally, we propose possible directions and methodologies for future prospectives in this field, as many aspects of the plant-Cd interaction remain to be discovered.