Photocatalysis offers a practical solution to the ever increasing energy and environmental issues by using a semiconductor to harvest freely available sunlight. Photoactive organic semiconductor nanocrystals (OSNs) are promising photocatalysts due to their structure and function which are easily tunable by molecular design. Extensive studies have yielded significant progress on OSNs in terms of photoresponse, charge carrier mobility, as well as photoconversion efficiency. This review provides a comprehensive discussion of the emerging crystal and interface engineering strategies used in optimizing structure/property of OSNs. The basic mechanisms involved in organic photocatalysis are discussed, for a better understanding of its dependence on the molecular and supramolecular structures. Then, the intermolecular interactions in molecular packing and the kinetic and thermodynamic control over the crystal growth process are summarized, with the aim of tuning the optical and electrical properties. Band energy alignment, charge carrier dynamics, and charge transfer are discussed in different heterostructures. In each case, structure/property relationships and how to tune them are emphasized. Finally, challenges and opportunities for the practical use of the organic photocatalysts are discussed. Precise control of the structure/property in photocatalytic organic nanocrystals is still an unresolved challenge. Relevant molecular crystal engineering strategies are reviewed by discussing the interplay of different intermolecular interactions and the kinetic and thermodynamic considerations to attain good structure/property control. To fulfill all the property requirements, interface engineering strategies are also used to design high‐efficiency and stable organic photoconversion systems.