Maintenance of metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more metal cofactors. Human fungal pathogens acquire essential metal micronutrients like copper and iron from their environment, but due to their redox activity, these metals can become toxic if misappropriated. We show that the opportunistic fungal pathogen Candida albicans becomes sensitized to both Cu limitation and Cu elevation during treatment with the antifungal drug fluconazole, a mainstay in antifungal therapy. Adaptation to fluconazole stress by C. albicans involves an extensive remodeling of metal homeostasis networks, responses that are impacted by Cu availability in the growth environment. Our findings offer a new perspective for thinking about fungal response to drug stress that pushes cells out of their metal homeostatic zones, leading them to enact metal-associated adaptation mechanisms to restore homeostasis to survive.