Screw pine (Pandanus tectorius) leaf extract (PLE) has been shown to improve the tolerance of the White-leg shrimp Penaeus vannamei to various biotic and abiotic stressors. This study was a continuum to highlight the remarkable effects of this coastal plant extract in safeguarding brine shrimp Artemia franciscana, an important larval live food organism in aquaculture, from lethal heat, acidity, and salinity stress assays. Axenic Artemia nauplii were used to examine the impact of abiotic stress on the organism without being affected by microbial contamination. This approach provides greater clarity into the detrimental impacts of these stressors and allows for a more precise understanding of the molecular responses of Artemia to PLE. Exposure to 1–6 g/L PLE for 2 h was nonlethal to Artemia nauplii, with 5–6 g/L PLE demonstrated the highest protection against all three abiotic stressors, where survival increased by at least 22% as compared with the nonPLE-exposed control. Comparative transcriptome analysis revealed that multiple genes related to chitin-based cuticle (insect cuticle proteins, chitin-binding domain type 2, and structural constituent of cuticle proteins), carbohydrate metabolism (alpha-amylase, dihydrodiol dehydrogenase, and V-type H+-transporting ATPase subunit C), and the stress and innate immune responses (spaetzle, C-type lectin, CD109, major facilitator superfamily proteins) were differentially expressed. This study highlights the functional roles of PLE as a potential antistress agent in mitigating stress caused by environmental factors in farmed shrimp, promoting better health and resilience during aquaculture.