There are many publications over the past 20 years comparing nano-nutrients with their traditional forms. Differently, this study examined the effect of applying nano-Fe and nano-Zn—in two different ways (foliar and soil application)—on sugarcane development, yield, and mineral status using a greenhouse experiment at the National Research Centre. The study results of first yield (plant cane crop) showed that nano-Fe caused an increase in plant height, number of leaves, fresh weight (FW) of leaves, FW of stalk, and total FW by 5.3%, 20.3%, 38.0%, 27.4%, and 33.3%, respectively, compared to nano-Zn. Despite the majority of growth metrics showed to be improved by using either of the two nano-sources, both nano-Fe and nano-Zn have been demonstrated to negatively impact nutrient ratios. The foliar application method was found to be superior, and the second application of nano-Zn to soil effectively halted the growth of all treated replicates. The data of the first ratoon (second yield) showed that FW of leaves, FW of stalk, total FW, and dried weight (DW) of stalk followed one trend line (nano-Fe–soil > control-foliar (sprayed distilled water) > nano-Zn-foliar > nano-Fe-foliar > control-soil (distilled water added to soil)). In conclusion it can be noticed that using nanoparticles as a fertilizer could be a weapon with double-edges, since this may induce unexpected harmful effects. It is recommended to conduct additional research to comprehend the mechanisms underlying why a nano-source that benefits plants may harm them after the second addition.