4-1BB and CD40 agonists are promising candidates for cancer immunotherapy but have had limited success due to systemic toxicity risk. We generated a 4-1BB×CD40 bsAb (BCG021) with a more reasonable affinity. BCG021 demonstrated conditional 4-1BB and CD40 agonistic activity and did not show a bell-shaped response as observed for benchmark bsAb. Moreover, BCG021 also exhibited superior in vitro and in vivo efficacy, with ideal physiochemical properties and a better PK profile than the benchmark.