The 21st century demands a workforce and citizenry equipped with a dynamic set of skills beyond traditional academic knowledge. This paper examines the role of pedagogical strategies in fostering these critical 21st-century skills within secondary schools in Nigeria, ultimately aiming to enhance the quality of education. Drawing on a comprehensive literature review, this study explores various pedagogical approaches such as project-based learning, collaborative learning, technology integration, and critical thinking methodologies, and their potential to cultivate skills like critical thinking, creativity, communication, and collaboration (the 4Cs). It also critically analyzes the current state of secondary education in Nigeria, identifying challenges and opportunities for implementing these innovative strategies. The paper posits that a deliberate shift from traditional teacher-centered instruction to more learner-centered, engaging, and skills-focused pedagogies is essential for preparing Nigerian students to thrive in a rapidly evolving global landscape. Recommendations include policy reforms, extensive teacher professional development, provision of adequate resources, and a re-evaluation of curriculum and assessment practices to align with 21st-century learning demands.