Asia's highest ranked player, Nishikori leads a strong field despite the withdrawal of high-profile players such as Juan Martin del Potro and Milos Raonic.
The latter two both occupy spots in the world's top 14 but the Argentinian was forced to pull out due to a persistent wrist injury while Canada's Raonic cited a lack of fitness.
Their absence will likely bolster Nishikori's hopes of landing a first title in Malaysia, with the US Open finalist having previously gone close with semi-final appearances in 2011 and 2012.
Ahead of his fourth appearance at the ATP 250 hard-court event, the Japanese world number eight is eager to impress, especially with Asian great and coach Michael Chang in attendance.
"I always love to come back to Malaysia," Nishikori said.
"They have a great stadium [and a] good crowd. I've not won the tournament, so it's going to be my goal to win it.
"I hope I can do well in Kuala Lumpur, especially in front of Michael who had so much success in Asia and I hope a lot of the crowds come out to support me.
"Hopefully it is going to be a great tournament [for me]."
World number 13 Ernests Gulbis will hope to shake off a disappointing US Open, where he bowed out at the second round to Dominic Thiem, and will begin his tournament in Malaysia against a qualifier.
Since reaching the French Open semi-finals, Gulbis has not won back-to-back matches - taking in five tournaments' worth of competition.
Leonardo Mayer, Julien Benneteau and Pablo Cuevas make up the remainder of the top five seeds.
Defending champion Joao Sousa has positive memories of the competition, after winning his maiden ATP World Tour title in Kuala Lumpur last year, and will begin his defence against Benjamin Becker of Germany.
Becker won the pair's only previous meeting at the Topshelf Open earlier this year.
Making up the remainder of the seeds are Pablo Andujar of Spain and Australia's Nick Krygios - the latter capping off an impressive breakthrough season in the Malaysian capital.