Inorganic phosphate (Pi) and Zinc (Zn) are an essential macro- and micronutrients for plant survival. Control of Pi and Zn content in tissues is of major importance for normal plant growth and development. Zn deficiency typically leads to Pi over-accumulation in shoots (and vice versa), signifying the presence of complex interactions that link the homeostatic regulation of these two nutrients. Despite their primary importance, the molecular bases of these interactions remains poorly understood. Recent research has placed the co-regulation of these two elements at a limiting step in Pi and Zn distribution within plants, e.g. the loading of Pi and Zn into root xylem. In Arabidopsis thaliana, this process mainly involves members of the Phosphate 1 (PHO1 and PHO1;H1) family (for Pi) and the heavy metal ATPases protein (HMA2 and HMA4) family (for Zn). This review examines recent progress in determining the molecular mechanisms that regulate the loading of Pi and Zn into root xylem, by individually describing these specific genes. The first molecular evidence for their signalling crosstalk at this particular step of their transport in plants is also presented, with an emerging role for PHO1;H3. This recent progress is important for biotechnological and agronomic strategies aimed at enhancing Pi and Zn transfer to the aerial part of plants.