Effects of learner- and material-related factors on multimedia learning have mostly been investigated in isolation or partially. Moreover, studies on the text-picture multimedia document assess learning with a focus on retention and transfer rather than on comprehension, as it is the case in text processing research. This work focuses on manipulations of text and pictures, to support comprehension of factual instructional multimedia documents, particularly for struggling readers. Through the course of three experiments, using three different documents, with static or animated pictures, we explored what defines a reader of a multimedia document as struggling, and how text cohesion and cross-representational signaling affected their comprehension. We also studied the role of interest raised by the document on multimedia learning. Results showed that both learner- and material-related factors have an active role in multimedia learning, and should be considered with care when designing text-picture documents.