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The extent to which different agricultural strategies may affect the uptake of potentially toxic elements (PTEs) by cropped plants is not entirely understood at a field scale. This study addresses the effect of seasonality, Trichoderma inoculation alone, or combined with different applications of commercial-grade clinoptilolite (i.e., foliar action, fertigation, and pellet) on the PTE content of early- and late-ripening cultivars of Cucumis melo L. Two similar field experiments were performed in spring and summer. For each cultivar/treatment combination, the input of PTEs [namely, chromium (Cr), copper (Cu), and lead (Pb)] into the soil-crop system through irrigation water, fertilizers, pesticides, and treatment products (i.e., Trichoderma and clinoptilolite products), as well as the PTE content of melon stem, leaves, and fruit, were measured through inductively coupled plasma-optic emission spectrometry (ICP-OES). Neither Trichoderma alone nor with clinoptilolite had a visible effect on PTE uptake by plants, whereas early season cultivation was strongly associated with reduced uptake of Cu and Pb. The high correlation of Cu and Pb content with stem and leaf calcium (Ca) content (used as a proxy for different transpiration rates under different growing seasons) indicated a possible uptake of these metals through Ca nonselective cation channels as a defense against drought stress. Reduced Cu and Pb concentrations were found in early-ripening fruit cultivated in spring. Concerning Cu and Pb risk management, in case of significant contamination in Mediterranean calcareous soils, early-ripening Cucumis melo L. cultivars are suggested instead of late-ripening ones.