Culturally Responsive Teaching (CRT) is a learning approach adopted by the Indonesian government to improve the quality of education in the face of global challenges, so that students can apply their knowledge in daily life while developing 21st-century skills. This approach is particularly relevant in Maluku, which possesses a wealth of local culture that serves as a learning resource. This study aims to analyze 21st-century skills and teachers’ understanding of these skills in CRT-based Physics science lesson planning that is integrated with the local wisdom of Maluku. The study employed a content analysis design on 18 Physics science instructional documents (lesson plans/teaching modules) to identify the integration of 21st-century skills, which encompass the four Cs—Communication, Creativity, Critical Thinking, and Collaboration—based on 18 indicators using a 1–4 rating scale. In addition, interviews were conducted with two pre-service teachers and five teachers who received the highest scores for integrating 21st-century skills into their instructional planning documents. The research results show that all 21st-century skills analyzed are still in the “has not yet achieved competency” category with an average score of 1.01, consisting of Creativity (1.00), Critical Thinking (0.83), Communication (0.78), and Collaboration (1.44). Most teachers and prospective teachers share a relatively similar understanding of the importance of 21st-century skills and the need to integrate these skills into instruction. The main challenge they face is linking local wisdom to concepts in physics so that students can easily understand them, as well as teachers’ still limited understanding of the types of local wisdom that can be integrated into the learning process.