Organic solar cells (OSCs) present a promising renewable energy technology due to their cost‐effectiveness, adaptability, and lightweight nature. The advent of non‐fullerene acceptors has further boosted their significance, allowing for power conversion efficiencies that surpass 19% even with an active layer thickness of about 100 nm. However, in order to achieve large scale production, it is necessary to fabricate OSCs with thicker active layers exceeding 300 nm that are compatible with large‐area printing techniques. Nevertheless, OSCs with thick active layers have inferior performance compared to those with thin active layers. To expedite the transition of OSCs from laboratory to industrial high‐throughput manufacturing, considerable efforts have been made to comprehend the performance limitations of thick active‐layer OSCs, develop novel photoactive materials that are high‐performance and tolerant towards the thickness of the active layer, and optimize the morphology of the photoactive layer and device structure. This review aims to provide a comprehensive summary of the mechanisms that lead to efficiency loss in thick active‐layer OSCs, the representative works on molecular design, and the optimization strategies for high‐performance thick active‐layer OSCs, and the remaining challenges that must be addressed.This article is protected by copyright. All rights reserved.