As skilled readers, we move smoothly from learning to read, to reading to learn. However, for students with literacy difficulties, achieving the end goal of reading comprehension may be a herculean task. Proficient reading skills are essential not only for reading and writing, but also for accessing, understanding and synthesising information across all subjects. In this chapter, we delve into the Science of Reading to understand the diverse needs of these students. The chapter also explores how educators can support struggling readers through a multifaceted approach, involving high-leverage practices (HLPs) and evidence-based strategies within a tiered system of support (TSS). The TSS is widely adopted in Singapore, where quality classroom instruction forms the foundation at Tier 1, with nation-wide programmes providing literacy support at Tiers 2 and 3. However, to enhance the effectiveness of the TSS, it is paramount for teaching and learning across the tiers to be cohesive and aligned.