In this empirical study we examined the effect of a literacy-infused science intervention on fifth grade economically challenged students' science achievement in the curriculum-based and standardized assessments. A total of 27 treatment students and 20 comparison students from two intermediate schools in a rural district in South Texas in the United States participated in the present study. The intervention consisted of ongoing, structured, bi-weekly virtual professional development (VPD) with virtual mentoring and coaching (VMC) at the teacher level and literacy-infused science lessons with inquiry-based learning delivered at the student level. Results revealed a significant and positive intervention effect in favor of treatment students as reflected in higher normal curve equivalent scores in the standardized science assessment and higher scores in curriculum-based assessment. We conclude that the literacy-infused science intervention, inclusive of evidence-based curriculum, VPD, and VMC, is particularly beneficial for promoting science learning for the students in rural areas with educational and economical challenges due to geographic isolation.