<p>Innovation and entrepreneurship increasingly take place in culturally diverse environments, yet research on how cultural dynamics interact with design-led entrepreneurial practices remains fragmented. This study conducts a systematic literature review (SLR) of 90 peer-reviewed articles published between 2010 and 2025 to examine how cross-cultural innovation and design-led entrepreneurship are conceptualized, how they intersect, and what outcomes emerge from their integration. Using a structured search strategy across Scopus and Web of Science and applying thematic synthesis, the review identifies five core themes: cultural diversity and collaboration, design-thinking integration in entrepreneurship, innovation practices in cross-cultural contexts, entrepreneurial strategies in diverse markets, and market-oriented adaptation. The findings show that cultural diversity expands cognitive resources, while design-thinking processes help organize this diversity into actionable innovation pathways. The integration of cultural insight and design-led methods enhances creativity, contextual relevance, and market adaptability, resulting in improved innovation and entrepreneurial outcomes. However, the review also highlights gaps, including limited theoretical integration and a lack of measurement tools for assessing cultural–design alignment. This study contributes a synthesized foundation for advancing theory and practice in this emerging domain and outlines key directions for future research.</p>