A new Oncoscience perspective maps the 2025–2026 glioblastoma clinical trial pipeline across four mechanistic domains, highlighting how developers are increasingly pairing biomarker-selected patients with rational combinations. The analysis frames a shift away from broad, one-size-fits-most approaches toward molecularly anchored trial designs. The pipeline overview emphasizes that patient selection—using tumor and microenvironment markers—has become central to study structure, with combination logic focused on overcoming resistance pathways rather than simply escalating single-agent potency. The review also underscores how trial activity is concentrating around actionable tumor biology. For industry teams, the work signals that future glioblastoma assets may face more competitive bar-setting around companion diagnostics, enrollment strategy, and combination feasibility. It also suggests that developers planning next studies need to align target validation, biomarker strategy, and combination rationale early. Overall, the perspective captures a durable pattern in neuro-oncology: trial execution is being redesigned around measurable selection criteria and mechanism-based combinations designed to sustain response.