Post-translational modifications of ribosomal proteins are pervasive in eukaryotes, yet their mechanistic contributions to ribosome function remain poorly understood. Saccharomyces cerevisiae encodes ten dedicated ribosomal protein methyltransferases, each targeting specific residues across the 40S and 60S subunits. To interrogate the functional consequences of these modifications, we established a high-resolution two-dimensional size-exclusion chromatography–mass spectrometry (2D-SEC-MS/MS) workflow capable of reproducibly resolving native ribosome populations and quantifying subunit composition at scale. Systematic profiling of knockout strains revealed only subtle perturbations in polysome to monosome and 60S to 40S ratios and no substantial reorganisation of core stoichiometry or paralogue abundance, indicating that methylation does not broadly remodel ribosomal architecture. In contrast, phenotypic assays uncovered a striking and unexpected pattern: All knockouts displayed enhanced tolerance to Ni²⁺, Cu²⁺, and other transition metals. Motivated by these findings, we are integrating inductively coupled plasma mass spectrometry (ICP-MS) of purified polysomes to directly quantify metal - ribosome interactions and determine whether loss of methylation alters metal-binding affinity. Complementary thermal and solvent proteome profiling will assess how methylation influences ribosomal stability under metal stress. Together, these approaches reveal a previously unrecognised functional axis in which discrete methyl marks fine-tune ribosome metal interactions to modulate translational output in fluctuating environments. Our work may help establish ribosomal protein methylation as a key determinant of metal-dependent structural plasticity and provides a mechanistic framework for understanding how ribosomal specialisation supports cellular adaptation to stresses.