This study analyzes the collaboration between design and entrepreneurship students through a Challenge-Based Learning approach. Students from both disciplines worked in teams to address real-world challenges presented by an academic partner. The challenge was structured in four stages: situational analysis, opportunity assessment, solution proposal design, and planning and communication. During five weeks students learned about diverse topics and received guidance from professors so they can have all the required information to solve the challenge. A post-survey assessed the role of problem-solving, entrepreneurship, and collaboration skills. Regression analysis showed the importance of collaboration in enhancing problem-solving abilities. Design students reported gaining business knowledge such as market analysis and financial planning, while entrepreneurship students learned design tools and prototyping methods. Overall, the experience was considered valuable and meaningful, as students developed diverse skills and knowledge across disciplines. The Challenge-Based Learning approach proved effective in preparing students to face real-world problems.