The human tumor microenvironment is a unique bionetwork of heterogeneous collection of tumor cells along with different kind of immune cells, myeloid cells, lymphocytes, and a repertoire of signaling molecules. Approaches so far resulting into standard of care have met with limited success owing to several different factors including, but not limited to, access to the TME, heterogeneity of mechanisms involved with tumors, amongst others. Through rigorous biomarker analyses and artificial intelligence (machine learning) we aim to identify and establish the right immunotherapy for the right patient populations that would boost treatment outcomes. Targeting the immune cell engager pathways our HBICE approach is directed towards combining early and late stage immune engagers to prime and target the tumors for immediate and complete elimination. With a multi-pronged antibody (HBICE) approach to identify novel targets and mechanisms with in the TME, our goal is to transform cancer treatment paradigm by enabling the body’s own immune system to attack these tumors and bring long-term benefits to patients.