*Result*: Programming Smectic Soft Defects via Pixelated Holographic Lithography.
*Further Information*
*The molecular ordering and defects in self‐assembled soft matter systems are pivotal to their functionality and the advancement of innovative applications. However, achieving precise guidance in the assembly and dynamical modulation of defect structures in an artificial manner remains a formidable challenge in soft matter and interdisciplinary science. Herein, a digitally controlled pixelated holographic lithography system is established to fabricate nanoscale surface reliefs, enabling precise manipulation of smectic liquid crystal lamellar defect structures. These surface reliefs, with customizable topographic features, facilitate versatile smectic soft defect engineering, allowing selective assembly of square focal conic domains and oily streak defects, along with precise control over their periodicity, orientations, and patterned coexistence within micro‐regions. The defect structures demonstrate exceptional stability and durability under UV irradiation, providing a robust framework for versatile defect engineering. This work opens a new pathway for manipulating lamellar superstructures in soft matter, offering potential applications in advanced functional materials and devices. [ABSTRACT FROM AUTHOR]*