This systematic review addressed the following question: Which are the relations between L1 and/or L2 foundational and upper-level language skills, cognitive skills, high-order cognitive and self-regulation factors and L2-English reading comprehension skills in 11-to-19 year EFL secondary school students with different L1 language profiles? Following preferred reporting items for systematic reviews and meta-analyses guidelines, twenty-seven studies were included for a systematic synthesis of results in the light of the different grades of "family language distance" between L1 and L2-English (i.e., "close related" vs. "partially related" vs. "not related"). We found that several L1 and L2 language skills (e.g., vocabulary, morphological awareness), cognitive skills (e.g., working memory) and high-order factors as metacognitive knowledge were positively associated with L2-English reading comprehension, regardless of different language groups. Conversely, we found that several well-known predictors of text comprehension are neglected in the scientific literature on reading in L2. We discuss practical implications and key recommendations to support school and future research.