Background and Objectives: Cell-free immune-conditioned products can preserve biological complexity while enabling standardized manufacture, repeated low-volume administration, and mechanism-linked testing. This review developed a source-aware framework for their translation in advanced solid tumors. Materials and Methods: PubMed/MEDLINE, consensus statements, profession-al-society documents, regulatory resources, and reporting guidelines were reviewed through 2 August 2026 across clinical context, source architecture, product class, ana-lytical quality and potency, membrane microdomains, intradermal delivery, New Ap-proach Methodologies (NAMs), and evidence governance. Seventy-one references in-formed a SANRA-aligned qualitative synthesis. Results: The framework separates biological source from recovered composition; de-fines extracellular lipid-protein matrix as a neutral family term and phospholipopro-teomic matrix as an evidence-dependent descriptor; and specifies identity, purity, re-sidual, potency, stability, and comparability requirements. Microdomain reconstruc-tion is operationalized through reproducible architecture, target-membrane interac-tion, structural reorganization, causal immune function, and prospective human con-firmation. A seven-publication evidence lineage demonstrates experimental tractabil-ity across product definition, immune-fingerprint preservation, stability, monitoring, functional profiling, traceability, and mechanistic synthesis. The review also specifies a minimum prospective intradermal administration and feasibility dataset, NAM con-texts of use, a three-module clinical architecture, a claim-to-evidence ladder, and a staged validation roadmap. Conclusions: This framework links product identity, mechanism-linked potency, in-tradermal feasibility, human biological engagement, multidomain clinical assessment, and comparative validation.