Thanks for your insights @Stanislav Zhelyazkov .
Hi @Dean Gross ,
In addition to @Stanislav Zhelyazkov 's insights, the short answer to your question is NO – today Azure Lighthouse cannot be used with Defender Security Center and M365 Security Center directly.
This is because Azure Lighthouse only supports requests that are handled by Azure Resource Manager. Per our documented limitations, the operation URIs for these requests should start with https://management.azure.com . As you can see from the screenshots below, the URI for M365 security center starts with https://api.security.microsoft.com and is hence not supported directly today.
However, it is possible to manage the security of O365 environments from Azure Lighthouse using Azure Sentinel as documented here.