Resilience to directional climate change depends on a specie’s evolutionary potential and phenotypic plasticity. An insufficient understanding of the relative importance of both factors, however, hinders our ability to predict future performance. We combined intermittent-flow respirometry and RNA-sequencing to quantify how genetically distinct spotted seatrout populations respond to thermal challenge, and genotyping-by-sequencing to look for genomic signatures of selection. Fish from the northern population of spotted seatrout exhibited standard metabolic rates up to 35% higher than their southern counterparts when measurements were made at the same temperatures (ranging from 5°C to 30°C). Differential gene expression analyses revealed both shared and unique gene sets were expressed in both populations in response to thermal stress. Annotations of differentially expressed genes give insight into the common and different molecular pathways involved in responses to thermal stress. FST-based analyses of genomic data identified 40 single nucleotide polymorphisms (SNPs) as outliers, which are putative targets for directional selection. Annotations of these outlier loci revealed homologs with predicted functions in transcription regulation, cell cycle control, and cellular transport. These results advance our understanding of population-specific differences in spotted seatrout which can be incorporated into mechanistic models to predict their resilience directional climate change.