Multispecific and multivalent antibodies are seen as promising cancer therapeutics and numerous antibody fragments and derivatives have been developed to exploit the avidity effects that result in increased selectivity for cancer cells. Examples include CovX-bodies, in which two targeting peptides are fused to an antibody scaffold, and BiTE antibodies, which comprise a single-chain bispecific antibody. Chemical peptide synthesis and chemoselective ligations can also be used to generate a variety of molecules with different numbers and combinations of binding moieties in a modular and homogeneous fashion. In this study, we synthesized a series of targeted ‘immune system engagers’ (ISErs) using solid phase peptide synthesis and chemoselective ligations. To explore avidity and valency effects, we constructed ISErs bearing different numbers and combinations of two ‘binder’ peptides that target ephrin A2 and integrin α3 receptors and an ‘effector’ peptide that binds to formyl peptide receptors and stimulates an immune response. We investigated various synthesis strategies for generating multivalent and multispecific ISErs and studied their activities in terms of binding to cancer cells and stimulation of immune cells. This study gives insights into receptor distribution on cancer cells and avidity and valency effects for the design of potential anti-cancer therapeutics.