In this paper, we design a frame structure for unique word (UW) based transmission of multiple-input-multiple-output (MIMO) systems under doubly-dispersive wireless channel conditions. We elaborate an energy and spectral efficiency analysis of a MIMO UW-based system vs. a conventional MIMO cyclic prefix (CP)-based system. Considering the UW-based transmission for a MIMO multi-carrier, we derive its signal processing algorithms for channel estimation and joint channelequalization-and-demodulation. Through theoretical derivations as well as extensive simulations, we show that the proposed MIMO UW-based system significantly outperforms the state-ofthe-art approaches. I. INTRODUCTION T OWARDS the sixth generation (6G) cellular networks, new applications and use-cases are being enabled for the vertical markets, while also new challenges for a holistic approach and more efficient service provisioning are being defined. Thanks to the flexible physical layer definitions in latest release of fifth generation (5G) New Radio (NR) [1], diverse services namely enhanced-mobile-broadband, ultrareliable-low-latency-communication, and massive machinetype-communication are envisioned to coexist within the same time interval and the same frequency band. A major advancement for realizing this coexistence is the massive multipleinput multiple-output (MIMO) technology which can be used for three key concepts, i.e., beamforming, spatial diversity and spatial multiplexing. While employing the MIMO technology for spatial diversity or spatial multiplexing, the mobility of the users becomes limited because a large number of channel parameters requires a long training sequence that together with the data packet, must fit within the channel coherence time. Unique-word (UW) transmission is a promising candidate that facilitates per-block synchronization and channel estimation [2], [3], [4]. The main concept is to replace the cyclic prefix (CP) of random nature by a deterministic sequence that is known to both transmitter and receiver. Hence, maintaining the advantages of CP in terms of robustness against multipath channels, UW allows fast channel tracking in highly mobile Manuscript