In many secondary classrooms, biology is still taught as a sequence of concepts to be memorized rather than as a living science for interpreting evidence, solving problems, and making responsible decisions. Meanwhile, education systems increasingly demand that learners develop critical thinking—interpreting information, analyzing claims, evaluating evidence, inferring conclusions, and reflecting on reasoning quality—skills strongly associated with scientific literacy. Project-Based Learning (PjBL) and integrated STEM education provide complementary pathways to develop these competencies. PjBL organizes instruction around an authentic driving question and a sustained inquiry process culminating in a public product, while integrated STEM positions science and mathematics as anchor disciplines and uses engineering design and technology as connective practices. This article synthesizes research evidence and theory up to 2024 to argue for the urgency of STEM-integrated PjBL in biology learning as an instructional strategy to improve students’ critical thinking. Using a framework-synthesis method, we integrate (1) critical thinking constructs (Delphi consensus and related frameworks), (2) empirical and meta-analytic evidence on PjBL and STEM in science learning, and (3) biology-specific affordances (systems, modeling, and socioscientific issues). Results are presented as an explanatory model linking STEM-PjBL design features to learning mechanisms and critical thinking outcomes, an evidence map, a practical project design template, and an assessment blueprint. The synthesis indicates that PjBL can promote critical thinking compared with traditional instruction, and that STEM-integrated variants add value by increasing the need for data-based reasoning, quantitative modeling, optimization, and design justification. We conclude with implementation guidance for teachers and school leaders, including scaffolding strategies, equity safeguards, and documentation approaches for credible reporting of learning outcomes.