Vendor-neutral body vs. platform vendor
The CISSP is issued by ISC2, a vendor-neutral nonprofit whose Common Body of Knowledge is deliberately independent of any single technology. SC-500 is issued by Microsoft as part of its role-based certification track, and it tests the Microsoft security stack specifically — Defender, Entra, Purview, Sentinel, and AI workload protection.
That difference sets the tone for everything else: the CISSP proves you understand security principles anywhere, while SC-500 proves you can operate one vendor's tools well.