Nutrient supplementation can bypass genetic deficiencies, but the underlying mechanisms behind this metabolite-suppression are poorly understood. To explore how organisms compensate for genetic defects, we conducted a suppressor screen in Caenorhabditis elegans, which require dietary heme for survival. The multidrug resistance protein MRP-5/ABCC5 is essential for heme export, and its loss is lethal unless rescued by heme supplementation. Here we show, by screening over 160,000 haploid genomes in mrp-5 mutants, that suppressor mutations in Adaptor Protein (AP)-3 restore viability. Normally, heme is either exported or stored in lysosome-related organelles (LROs) where HRG-1 facilitates cytosolic transfer. In mrp-5 mutants, heme accumulates in LROs, degrading HRG-1 and depleting extra-intestinal tissues. Loss of AP-3 prevents HRG-1 degradation and redirects SLC49A3, a previously uncharacterized transmembrane protein, for heme export. Our findings highlight the role of vesicular dynamics in heme transfer offering insights into mechanisms of interorganellar heme trafficking and adaptation to nutrient limitations.