The plant ionome varies both inter- and intraspecifically despite the highly conserved roles for particular elements across the plant kingdom. Element storage requires transport across the plasma membrane and commonly deposition within the central vacuole. Therefore, tonoplast transport characteristics can be highly influential in controlling the plant ionome. As a result, individual cell types of the same plant, each with unique transcriptomes and vacuolar proteomes, can display very different elemental profiles. Here we address the use of natural variation in Arabidopsis thaliana for identifying genes involved in elemental accumulation. We present a conceptual framework, exploiting publicly available leaf ionomic and transcriptomic data across 31 Arabidopsis accessions, that promises to accelerate conventional forward genetics approaches for candidate gene discovery. Utilizing this framework, we identify numerous genes with documented roles in accumulation of calcium, magnesium and zinc and implicate additional candidate genes. Where appropriate, we discuss their role in cell-specific elemental accumulation. Currently, this framework could represent an alternate approach for identifying genes suitable for element biofortification of plants. Integration of additional cell-specific and whole-plant ‘omics’ datasets across Arabidopsis accessions under diverse environmental conditions should enable this concept to be developed into a scalable and robust tool for linking genotype and phenotype.