Three methodological approaches were applied to understand the role of interest and self-efficacy in reading and/or writing in students without and with persisting specific learning disabilities (SLDs) in literacy. For each approach students in grades 4 to 9 completed a survey in which they rated 10 reading items and 10 writing items on a Scale 1 to 5; all items were the same but domain varied. The first approach applied Principal Component Analysis with Varimax Rotation to a sample that varied in specific kinds of literacy achievement. The second approach applied bidirectional multiple regressions in a sample of students with diagnosed SLDs-WL to (a) predict literacy achievement from ratings on interest and self-efficacy survey items; and (b) predict ratings on interest and self-efficacy survey items from literacy achievement. The third approach correlated ratings on the surveys with BOLD activation on an fMRI word reading/spelling task in a brain region associated with approach/avoidance and affect in a sample with diagnosed SLDs-WL. The first approach identified two components for the reading items (each correlated differently with reading skills) and two components for the writing items (each correlated differently with writing skills), but the components were not the same for both domains. Multiple regressions supported predicting interest and self-efficacy ratings from current reading achievement, rather than predicting reading achievement from interest and self-efficacy ratings, but also bidirectional relationships between interest or self-efficacy in writing and writing achievement. The third approach found negative correlations with amygdala connectivity for 2 reading items, but 5 positive and 2 negative correlations with amygdala connectivity for writing items; negative correlations may reflect avoidance and positive correlations approach. Collectively results show the relevance and domain-specificity of interest and self-efficacy in reading and writing for students with persisting SLDs in literacy.