Toxicogenomics offers a powerful means to characterize the molecular effects of environmental chemicals, often with reduced animal testing. Its use in human health assessment has grown rapidly in the last decade. In contrast, applications in ecological risk assessment remain limited, and uncertainty remains regarding how toxicogenomic responses translate to ecologically relevant outcomes. The objective of this research was to increase confidence in, and advance the application of, toxicogenomic approaches within ecological risk assessment. A landscape review was conducted to evaluate current toxicogenomic applications in ecological assessments and to identify existing regulatory considerations. The primary focus of research among identified applications was the development and evaluation of ecological transcriptomic points of departure (tPODs). Although regulatory agencies are beginning to consider toxicogenomic data within weight-of-evidence evaluations, no formal ecological risk assessment frameworks currently incorporate these data. The review identified three key research gaps: (1) alignment between qPCR-based and whole-transcriptome tPODs; (2) ability of transcriptomic approaches to resolve species-sensitivity differences; and (3) concordance of in vitro and in vivo transcriptomic responses. To address these gaps, a case study was designed using unpublished RNA sequencing and EcoToxChip qPCR datasets from fathead minnow and rainbow trout exposed to ethinylestradiol during early life stages. Comparative analyses will evaluate sensitivity, reproducibility, and variability across technologies, species, and exposure durations, and assess concordance with established apical effects and reference values. EcoToxChip data generated by a contract research organization will also assess feasibility outside academic and governmental settings. The case study will address the performance and limitations of transcriptomic new approach methods (NAMs), inform best practices for their use, and support their broader application in ecological assessments. Collectively, this work strengthens the evidence base needed to incorporate toxicogenomics into ecological risk assessment, and identifies priority areas for future research, including cross-trophic evaluations and applications in chemical grouping and read-across.