Mantle cell lymphoma (MCL) accounts for nearly 2-6% of all non-Hodgkin lymphoma (NHL) cases, with a steady incidence increase over the past few decades. Although many patients achieve an adequate response to the upfront treatment, the short duration of remission with rapid relapse is challenging during MCL management. In this regard, there is no consensus on the best treatment options for relapsed/refractory (R/R) disease, and the international guidelines demonstrate wide variations in the recommended approaches. The last decade has witnessed the introduction of new agents in the treatment landscape of R/R MCL. Since the introduction of Bruton\'s tyrosine kinase (BTK) inhibitors, the treatment algorithm and response of R/R MCL patients have dramatically changed. Nevertheless, BTK resistance is common, necessitating further investigations to develop novel agents with a more durable response. Novel agents targeting the B-cell receptor (BCR) signaling have exhibited clinical activity and a well-tolerable safety profile. However, as the responses to these novel agents are still modest in most clinical trials, combination strategies were investigated in pre-clinical and early clinical settings to determine whether the combination of novel agents would exhibit a better durable response than single agents. In this report, we provide an updated literature review that covers recent clinical data about the safety and efficacy of novel therapies for the management of R/R MCL.