This systematic review examines how integrating real and virtual laboratories supports inquiry-based learning (IBL) and the development of 21st-century competencies in science education. The ERIC, Education Source, and Scopus databases (2010–2025) were searched using PRISMA-aligned criteria to include peer-reviewed, English-language empirical studies published in the last fifteen years (2005–2025). Eighteen publications met the eligibility criteria. Across studies, hybrid laboratory designs generally outperformed single-modality approaches on conceptual understanding, inquiry processes, and procedural skills when sequencing and scaffolding were explicit. Three effective pedagogical patterns were identified: virtual-then-real to support conceptual understanding and manage cognitive load; real-then-virtual to consolidate learning and extend exploration; and integrated, within-session blending to iterate between concrete manipulation and abstract visualization. Teacher roles were pivotal, encompassing design (aligning modalities with inquiry goals), scaffolding (linking representations and practices), and adaptive facilitation (calibrating guidance over time). Common challenges included limited teacher preparation, suboptimal sequencing that contributed to cognitive overload, and resource constraints in under-resourced contexts. We propose design principles that specify purposeful sequencing, scaffolding, and assessment across modalities, alongside scalable professional development. The review offers actionable guidance for researchers, educators, and policymakers seeking inclusive, inquiry-rich hybrid laboratories that leverage the complementary affordances of physical and virtual environments.