As an adaptive response to exogenous stress, bacteria undergo rapid remodelling of lipid metabolism pathways to dynamically alter the lipid compositions of their cellular membranes. Here, using Escherichia coli (E. coli) as a well understood model system for metabolic adaptation in response to environmental stress (e.g., nutrient depletion), we report the development of a multi-omics analysis strategy for comprehensive quantitative monitoring of changes in lipidome and proteome profiles under exponential growth phase (EGP) versus stationary growth phase (SGP) conditions. We highlight the complementarity of shotgun- and LC-MS and -MS/MS based methods for lipidome analysis, as well as the necessity of using advanced workflows incorporating field asymmetry ion mobility spectrometry (FAIMS) for improving the coverage of low abundance lipid classes such as cardiolipin, and ultraviolet photodissociation (UVPD)-MS/MS for complete lipid structural characterization (e.g., cyclopropyl- and branched chain modifications within fatty-acyl chains) between the two conditions. We also demonstrate the utility of LC-MS/MS based proteomic analysis, in which we observe 85% of the predicted E. coli lipid metabolism enzymes, to uncover the specific enzymes responsible for the observed adaptive lipid metabolism response, as well as for identification of related metabolic pathway alterations involving global fatty acid synthesis and fatty acid degradation, and also to identify increases in the abundance of proteins which are protective against oxidative stress under the stationary phase growth conditions.